Breast cancer incidence trends in Golestan, Iran: An age-period-cohort analysis by ethnic region, 2004-2018.

BACKGROUND: We aimed to examine the effects of age, diagnosis year (calendar period) and birth year (cohort) on the incidence trends of breast cancer among Golestan women, Northeast Iran, 2004-2018. METHODS: Incidence data were obtained by residential status (urban/rural) and ethnic region (Turkmens/non-Turkmens). We calculated age-standardized incidence rates (ASRs) per 100,000 person-years. The estimated annual percentage change (EAPC) were calculated, and age-period-cohort (APC) models fitted to assess non-linear effects of period and cohort as incidence rate ratios (IRRs). RESULTS: The total number of female breast cancer cases in Golestan, 2004-2018, were 3853, with an overall ASR of 31.3. We found higher rates in urban population (40.5) and non-Turkmens region (38.5) compared to rural area (20.8) and Turkmens region (20.2), respectively. There were increasing trends in incidence rates overall (EAPC= 4.4; 95%CI: 2.2, 6.7), with greater changes in rural areas (EAPC=5.1), particularly among non-Turkmens (EAPC=5.8). The results of the APC analysis indicate the presence of significant non-linear cohort effects with increasing IRRs across successive birth cohorts (IRR=0.1 and IRR= 2.6 for the oldest and the youngest birth cohorts vs. the reference birth cohort, respectively). CONCLUSION: We found increasing trends in breast cancer incidence among Golestan women over the study period, with disparities in patterns and trends by residence area and ethnic region. The observed cohort effects suggest an increasing prevalence of key risk factors for breast cancer in this Iranian population. Further investigations are warranted to clarify the relationships between determinants such as reproductive factors and ethnicity in the region.

Colorectal cancer incidence trends in Golestan, Iran: An age-period-cohort analysis 2004-2018.

BACKGROUND: We investigated the effects of factors including age, birth year (cohort) and diagnosis year (period) on colorectal cancer (CRC) incidence trends in Golestan, Northeast of Iran, 2004-2018. METHODS: We obtained data on incidence cases of CRC from the Golestan Population-based Cancer Registry by sex and area of residence (urban/rural). Age-standardized incidence rates (ASRs) were calculated using the World standard population and presented per 100,000 person-years. We calculated the estimated annual percentage change (EAPC) with 95 % confidence intervals (95 % CI) fitted age-period-cohort (APC) models to assess non-linear period and cohort effects as incidence rate ratios (IRRs). RESULTS: Overall, 2839 new cases of CRC (ASR = 13.7) were registered in the GPCR over 2004-2018. Our findings suggested significantly increasing trends in CRC incidence rates from 2004 to 2018 (EAPC = 3.7; 95%CI: 0.4, 7.1), with the greatest changes occurring in rural women (EAPC= 4.7; 95%CI: 0.4, 9.2). We observed a strong cohort effect with a consistent increase in the IRR across successive birth cohorts, starting with the oldest birth cohort (1924) (IRR= 0.1 versus the reference birth cohort of 1955) through to the most recent cohort born in 1983 (IRR= 1.9). The largest cohort effects were found among rural females (IRR = 0.0, and IRR = 2.5 for the oldest and the youngest birth cohorts vs. the reference birth cohort, respectively). CONCLUSION: The increasing trends in CRC rates in Golestan are largely driven by generational changes in exposure to underlying risk factors. Further investigations are warranted to deliver effective prevention strategies for the control of CRC in Golestan.

Esophageal and gastric cancer incidence trends in Golestan, Iran: An age-period-cohort analysis 2004 to 2018.

Golestan province in the northeast of Iran is part of the Asian esophageal cancer belt and is known as a high-risk area for esophageal (EC) and gastric cancers (GC). Data on incident cases of EC and GC during 2004 to 2018 were obtained from the Golestan Population-based Cancer Registry (GPCR). The age-standardized incidence rates (ASRs) were calculated and presented per 100 000 person-years. The estimated annual percentage change (EAPC) with 95% confidence interval (95% CI) were calculated. We also fitted age-period-cohort (APC) models to assess nonlinear period and cohort effects as incidence rate ratios (IRRs). Overall, 3004 new cases of EC (ASR = 15.7) and 3553 cases of GC (ASR = 18.3) were registered in the GPCR. We found significant decreasing trends in incidence rates of EC (EAPC = -5.0; 95% CI: -7.8 to -2.2) and less marked nonsignificant trends for GC (EAPC = -1.4; 95% CI: -4.0 to 1.4) during 2004 to 2018. There was a strong cohort effect for EC with a consistent decrease in the IRR across successive birth cohorts, starting with the oldest birth cohort (1924; IRR = 1.9 vs the reference birth cohort of 1947) through to the most recent cohort born in 1988 (IRR = 0.1). The marked declines in EC incidence rates in Golestan relate to generational changes in its underlying risk factors. Despite favorable trends, this population remains at high risk of both EC and GC. Further studies are warranted to measure the impact of the major risk factors on incidence with a view to designing effective preventative programs.

Primary Biliary Tract Cancers in Golestan, Iran: 13-Year Experience of Golestan Population-Based Cancer Registry.

BACKGROUND: Epidemiological research on the high-risk population might be helpful in early detection and prevention of biliary tract malignancies. This study assesses the prevalence of biliary tract cancer (BTC) in the Golestan province, northeastern Iran, between 2004 and 2016. METHODS: The current study used information from the Golestan Population-based Cancer Registry (GPCR) to access the epidemiology of BTC across a 13-year period while taking into account temporal and geographic differences. The number of cases, crude rates, age-standardized incidence rates (ASRs) per 100,000 person-years, average annual percent change (AAPC), age-specific incidence rates, and 95% confidence intervals (CI) were reported for each year with respect to gender and place of residence. RESULTS: Totally, 224 instances of BTC overall (54% of whom were females) were reported throughout the research period. The ASR of BTC was 1.7 (95% CI: 1.4‒2) for females and 1.4 (95% CI: 1.1‒1.6) for men, respectively. Males exhibited a growing time trend in incidence (AAPC: 7.18; CI: 0.06‒14.81; P-value:0.048), whereas females had a decreasing trend (AAPC: 0.82; CI: -5.94‒4.57; P-value: 0.740). Both sexes saw an increase in age-specific incidence rates starting at the age of 45; however, males experienced a significant increase in incidence in the age group of 75 to 79 while the female rates grew steadily. CONCLUSION: The focus for cancer control in this region may be given to demographic groups with a combination of risk factors, including male gender, older age, and urban residence.

RT-LAMP in SARS-CoV-2 detection: point to improve primer designing and decrease molecular diagnosis pitfalls.

BACKGROUND: Due to the high transmission rate of SARS-CoV-2, diagnostic tests have become tools for identifying patients. The key points were the virus genomes survey to design RT-LAMP primers; comparing the sensitivity and specificity of RT-LAMP and RT-qPCR; and determining the relationship among clinical symptoms, CT scan, RT-qPCR, and RT-LAMP results. METHODS: This cohort study included 444 symptomatic patients. The specificity and sensitivity of RT-LAMP were assayed. The five statistical models, simultaneously, by RapidMiner to find the best method for detecting the virus were done through the correlation between the clinical symptoms, RT-LAMP, RT-qPCR, and CT scan results. The chi-square test by SPSS 26.0 was used to calculate kappa agreement. RESULTS: The virus genome was detected in all the positive samples (198) by RT-qPCR and RT-LAMP. In addition, 246 samples were negative by RT-qPCR, while 88 were positive by RT-LAMP. Data mining analysis indicated that there were most associations between the RT-LAMP and CT scan data compared to RT-qPCR and CT scan data. CONCLUSIONS: RT-LAMP could detect SARS-CoV-2 with great simplicity, speed, and cheapness. Therefore, it is logical to screen, a large number of patients by RT-LAMP, and then RT-qPCR can be used on the limited samples.

Development of an online cancer data collection and processing tool for population-based cancer registries in a low-resource setting: The CanDCap experience from Golestan, Iran.

BACKGROUND: Golestan Population-based Cancer Registry (GPCR) with more than 15-years experiences developed an in-house online software called Cancer Data Collection and Processing (CanDCap) to improve its data collection operations from the conventional offline method to new online method. We aimed to report the methods and framework that GPCR applied to design and implementation of the CanDCap. METHODS: CanDCap was designed based on International Agency for Research on Cancer (IARC) protocols and standards and according to the GPCR workflow. CanDCap has two parts including a web-based online part for data collection and a windows-based part for data processing consisting of quality control and deduplication of repeated records. Questionnaire for User Interface Satisfaction (QUIS) was used in order to assess user interaction satisfaction. RESULTS: CanDCap was implemented in 2018 and could improve the quality of the GPCR data during its first three years of activity (2018-2020), during which about 9,000 records were registered. The coverage for optional items including national ID, father name, address and telephone number were improved from 23 %, 32 %, 83 % and 82 % in conventional offline method (2015-2017) to 83 %, 81 %, 87 %, and 90 % after using the CanDCap (2018-2020), respectively. The timeliness was also improved from 4 years to 2 years. Overall, user interaction satisfaction was acceptable (7.8 out of 9). CONCLUSION: CanDCap could resulted in improvement in data quality and timeliness of the GPCR as a cancer registry unit with limited resources. It has the potential to be considered as a model for population-based cancer registries in lower-resource settings.

3-Dimensional Model to Study Apoptosis Induction of Activated Natural Killer Cells Conditioned Medium Using Patient-Derived Colorectal Cancer Organoids.

Natural killer (NK) cells are innate lymphocytes that can kill tumor cells via different pathways, including the secretion of cytotoxic granules in immunological synapses and the binding of apoptosis-inducing ligands with cognate death receptors on tumor cells. These ligands are also soluble in NK cells conditioned medium (NK-CM). However, novel preclinical in vitro models are required for solid tumors such as colorectal cancer (CRC) to investigate apoptosis induction of activated NK-CM in a tissue-like structure. In the present study, we established a patient-derived CRC organoid culture system as a new tool for CRC research in the last decade. Tumor organoids were stained with hematoxylin and eosin (H&E) and compared with the original tumor taken from the patient. Goblet cell differentiation and mucus secretion were evaluated using periodic acid-Schiff and alcian blue histochemical staining. Moreover, tumor organoids were stained for CDX2 and Ki67 markers with immunohistochemistry (IHC) to investigate gastrointestinal origin and proliferation. Histopathological evaluations indicated tumor organoids represent patient tumor characteristics. Primary NK cells were isolated and characterized using CD56 marker expression and the lack of the CD3 marker. Flow cytometry results showed the purity of isolated CD3-and CD56 + NK cells about 93%. After further ex vivo expansion, IL-2-activated NK-CM was collected. Secretions of IFN-γ and TNF-α were measured to characterize activated NK-CM. Cytokines levels were significantly elevated in comparison to the control group. Soluble forms of apoptosis-inducing ligands, including TNF-related apoptosis-inducing ligand (TRAIL) and FasL, were detected by western blot assay. Colon cancer organoids were treated by IL-2-activated NK-CM. Apoptosis was assessed by Annexin V-FITC/PI staining and quantified by flow cytometry. In conclusion, despite the activated NK-CM containing apoptosis-inducing ligands, these ligands' soluble forms failed to induce apoptosis in patient-derived colon cancer organoids. Nevertheless, we report a reliable in vitro assessment platform in a personalized setting.

Clinical Presentations of the Survivor and Non-survivor Hospitalized Patients with COVID-19 in the Golestan Province of Iran during the First Peak of the Epidemics.

Background: Considering the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, which causes coronavirus disease 2019 (COVID-19), we aimed to report the clinical features of 427 patients with COVID-19 and the outcomes after one-month admission to major teaching hospitals in the northeast of Iran. Materials and Methods: Data of patients hospitalized with COVID-19 from 20 February 2020 to 20 April 2020 was analyzed using the R software. The cases and their outcomes were monitored up to one month following their admission. Results: Among 427 patients with a median age of 53 years (50.8% male), 81 (19%) were directly admitted to the ICU ward, and 68 (16%) died during the study. The mean (SD) lengths of hospital stay were significantly higher in the non-survivors (6 (9) days) than survivors (4 (5) days) (P = 0.018). Ventilation need was reported in 67.6% of the non-survivors and 0.8% of the survivors (P < 0.001). Cough (72.8%), fever (69.3%), and dyspnea (64.0%) were the most common symptoms. There were more comorbidities in the severe cases (73.5%) and non-survivor (77.5%). Liver and kidney damage were significantly more common in non-survivors. Ninety percent of the patients had at least one abnormal chest CT scan finding, including crazy paving and consolidation patterns (27.1%), followed by the ground-glass opacity (24.7%). Conclusion: Results showed that the patients' age, underlying comorbidities, levels of SpO2, and laboratory findings at the time of admission may predict the progress of the disease and can be considered mortality-related factors.

Epidemiological and clinical characteristics of the COVID-19 epidemic and associated factors for mortality in Golestan province, Iran: a retrospective cohort study.

BACKGROUND: We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia and risk factors associated for mortality. METHODS: In this study, we included inpatient with acute respiratory distress syndrome at Golestan Hospitals who had been discharged or had died in 2020. Epidemiological, and clinical data were extracted from electronic medical records and compared between recovered and died cases. We used multiple logistic regression methods to explore the risk factors associated with in-hospital death. RESULTS: Overall 2,835 acute respiratory distress syndrome patients were included in this study, and 874 (30.83%) were positive for 2019-nCoV. Five hundred and sixty-three patients (19.86%) died, 1,687 patients (59.51%) were recovered. Of the total deaths, only 288 (10.15%) were attributed to COVID-19. The most common symptoms at onset of illness were respiratory distress [1,795 (63.32%)], fever [1,601 (56.47%)], dry cough [1,595 (56.26%)], sore throat [445 (15.70%)], and myalgia [342 (12.06%)]. One thousand and twelve (35.7%) had 1 or more coexisting medical conditions. In multiple logistic regression analysis, risk factors associated with the death included older age [OR (Odds Ratio) = 1.03; 95% CI; 1.02-1.04], blood oxygen level (SPO2 < 93%) (OR = 2.44; 95% CI; 1.79-3.31), comorbidities (OR = 2.15; 95% CI; 1.62-2.84), respiratory distress (OR = 1.74; 95% CI; 1.28-2.37), and headache (OR = 0.44 95% CI; 0.21-0.92). CONCLUSIONS: The 2019-nCoV infection caused collections of severe respiratory illness and was associated to a high ratio of hospitalization in ICU and high mortality. Older age and comorbidities were associated with more risk of death among patients with 2019-nCoV.

Mutational signatures in esophageal squamous cell carcinoma from eight countries with varying incidence.

Esophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence that is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries with varying incidence rates. Mutational profiles were similar across all countries studied. Associations between specific mutational signatures and ESCC risk factors were identified for tobacco, alcohol, opium and germline variants, with modest impacts on mutation burden. We find no evidence of a mutational signature indicative of an exogenous exposure capable of explaining differences in ESCC incidence. Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC)-associated mutational signatures single-base substitution (SBS)2 and SBS13 were present in 88% and 91% of cases, respectively, and accounted for 25% of the mutation burden on average, indicating that APOBEC activation is a crucial step in ESCC tumor development.

Analysis of Competing Risks of Causes of Death in Cancer Patients from Golestan, Iran over Twelve Years (2004-2016).

BACKGROUND: Cancer-related causes of death (cancer CoD) are the main etiologies of death in cancer patients. Recent increase in survival rates of cancer patients resulted in higher risk of dying from causes other than cancer, called competing causes of death (competing CoD). We aim to characterize competing CoD among cancer patients in Golestan province, Northern Iran. METHODS: Data on cancer incidence was obtained from the Golestan population-based cancer registry (GPCR) dataset. Data on causes of death was obtained from the Golestan death registry (GDR) dataset. Using a linkage method between the GPCR and GDR dataset, we prepared the study dataset including data on vital status and causes of death in our cancer patients. The proportions of cancer CoD and competing CoD were calculated. Multivariate logistic regression analysis was considered to assess the relationship between competing CoD and other variables. RESULTS: Overall, 4,184 cancer patients died in the study population, including 2,488 men (59.9%). Cause of death in 3,455 cases was cancer and 729 cases (17.4%) died due to competing CoD. Ischemic heart disease (40.7%) was the most common competing CoD in our population. Higher survival rate was the strongest variable related to the competing CoD (adjusted OR=1.91; 95%CI: 1.61-2.26). Residence area, age group and year of death were other indicators of competing CoD in our population. CONCLUSION: Our results suggest high rates of competing CoD in our cancer patients. Competing CoD should be mentioned in cancer control planning both in clinical practice as well as in public health policy making.
.

Building a Cancer Biobank in a Low-Resource Setting in Northern Iran: the Golestan Cancer Biobank.

BACKGROUND: We aim to present the development and the initial results of the Golestan Cancer Biobank (GoCB), in a low resource setting in northern Iran. METHODS: The GoCB protocol and its standard operation procedures (SOP) were developed according to internationally accepted standards and protocols with some modifications considering the limited resources in our setting. The main biological samples collected by the GoCB include blood sample, urine sample, fresh endoscopy tissue sample, fresh surgical tissue sample and formalin fixed paraffin embedded (FFPE) tissue sample. The GoCB collects patients' demographic data, tumor characteristics as well as data on risk factors. We developed a specific GoCB software for management of patient data and biological sample information. The GoCB dataset is annually linked with the Golestan cancer registry dataset to add complementary data (e.g., survival data). RESULTS: The GoCB started collection of data and biological samples in December 2016. By November 2020, a total number of 1217 cancer patients participated in the GoCB. The majority of the GoCB participants (n = 942, 77%) were those with gastrointestinal and breast cancers. Data on risk factors were successfully collected in 684 (56.2%) of the participants. Overall, 3563 samples were collected from the GoCB participants and 730 samples were used in 7 national and international research projects. CONCLUSION: We considered specific strategies to overcome major limitations, especially budget shortage, in the development and maintenance of a cancer-specific biological repositories in our setting. The GoCB may be considered as a model for the development of biobank in low- and middle-income countries (LMICs).

An intervention to increase hepatitis C virus diagnosis and treatment uptake among people in custody in Iran.

BACKGROUND: Iran is among countries with high opioid agonist therapy (OAT) coverage in prisons, which provides an infrastructure to increase feasibility of HCV programs. We aimed to evaluate the impact of an intervention to improve HCV screening, diagnosis, and treatment, including alongside the provision of OAT, in an Iranian prison. METHODS: During July-December 2018, in the Gorgan prison, all incarcerated adults (>18 years) received HCV antibody rapid testing and, if positive, provided a venepuncture sample for HCV RNA testing. Participants with positive RNA received direct-acting antiviral (DAA) therapy [(Sofosbuvir/Daclatasvir) for 24 or 12 weeks, respectively, for those with and without cirrhosis]. Response to treatment was measured by the sustained virological response at 12 weeks post-treatment (SVR12). RESULTS: Among 2015 incarcerated people with a median age of 35 years (IQR:29-41), the majority were male (97%), had not finished high school (68%), and had a history of drug use (71%), of whom 15% had ever injected drugs. A third of participants were receiving OAT, including 54% of those who had ever injected. HCV antibody prevalence was 6.7%, and RNA was detected in 4.6% of all participants; this prevalence was 32.6% and 24.7% among those with a history of injection, respectively. Treatment uptake was 82% (75/92) and was similar among people on OAT and those with a history of injection (81%). The majority completed treatment in prison and were available for SVR12 assessment (71%, 53/75). Achieved SVR12 was 100% (53/53) based on the available case analysis; those who did not have available SVR12 were released either prior to treatment initiation or completion (n = 39). CONCLUSION: The availability of OAT infrastructure should be considered as an opportunity for enhancing HCV care in prisons. Where resources are limited, the prison harm reduction network could be used to design targeted HCV programs among people who are at higher risk of infection.

Temporal and Geographical Trends of Incidence of Thyroid Cancer in Golestan, Iran, 2004-2013.

BACKGROUND: Thyroid cancer is the most common type of endocrine cancer. We aimed to determine the incidence rates of thyroid cancer across a 10-year period (2004-2013) in Golestan, Iran. METHODS: We obtained the thyroid cancer data from Golestan Population-Based Cancer Registry (GPCR). Age-standardized incidence rates (ASR) were calculated and reported per 100000 person-years. The Joinpoint software was used to assess time trends, and average annual percent changes (AAPCs) and their corresponding 95% confidence intervals (CIs) were reported. RESULTS: Of 326 registered patients, 83 (25.5%) were men and 243 (74.5%) were women. The mean age was 51.3 and 42.6 years for males and females, respectively. Overall, the ASR of thyroid cancer was 2.2 per 100000 person-year (AAPC = 2.76; 95% CI: -3.68 to 9.64). The test of co-incidence showed a statistically significant difference in the incidence of thyroid cancer between men (1.3) and women (3.2) (P < 0.001). According to our results, the ASR of thyroid cancer in western parts of Golestan is higher, including Gorgan and Aliabad cities. CONCLUSION: Increasing trends in incidence rates of thyroid cancer were found in the Golestan province during the study period, especially in women. We found significantly higher rates of thyroid cancer in women. Geographical diversities were seen in incidence rates of thyroid cancer in the Golestan province. Our results may be helpful for designing further researches to investigate the epidemiological aspects of thyroid cancer in the Golestan province.

Evaluation of Arylsulfatase D (ARSD) and long noncoding RNA ARSD-AS1 gene expression in breast cancer patients and their association with oncogenic transcription factors.

PURPOSE: Long non-coding RNAs (LncRNAs) are thought as tumorigenic factors in cancer progression. We investigated the clinical significance of arylsulfatase D (ARSD) and ARSD antisense in breast cancer patients. METHODS: Eighty breast cancer tumors were obtained from the Tumor Bank of Cancer Institute, Imam Khomeini Hospital. The expression level of ARSD and ARSD-AS1 were examined in breast tumors in comparison to the margin of normal tissues using quantitative real-time PCR. Demographic information and the clinicopathologic characteristics including tumor grade, presence of cell receptors, lymph node and vascular invasion were also evaluated. Bioinformatics databases were used for identification of ARSD and ARSD-AS1 molecular targets and their association with cancer. RESULTS: Significant up-regulation of ARSD was observed in tumor tissues in comparison with its antisense (p<0.05). Both ARSD and ARSD-AS1 expression in tumor specimens were notably lower than those in adjacent normal tissue. High expression of ARSD was associated to lower tumor grade (p<0.05). Bioinformatics results revealed the interaction of ARSD with STS and SUMF1 proteins was attributed to the inhibiting of sulfates activity. Also, ARSD co-expressed genes were associated with oncogenic transcription factors, MAF and GATA. TP53 transcription factor site was identified as a target of ARSD-AS1 mRNA. The interaction of this antisense with microRNA (miR-618) could explain its participation in tumor cell proliferation. CONCLUSION: Low expression of ARSD was associated with higher tumor grade. The evidence from this study enhance our understanding of ARSD and ARSD-AS1 function in cancer gene therapy. Accordingly, they could be introduced as great potential targets for breast cancer treatment.

A simple risk-based strategy for hepatitis C virus screening among incarcerated people in a low- to middle-income setting.

BACKGROUND: Hepatitis C virus (HCV) is among the highest priority diseases in custodial settings; however, the diagnosis remains suboptimal among people in custody. This study aimed to validate a short survey for identifying people with HCV infection in a provincial prison in Iran. METHODS: Between July and December 2018, residents and newly admitted inmates of Gorgan central prison completed a questionnaire, including data on the history of HCV testing, drug use, injecting drug use, sharing injecting equipment, and imprisonment. Participants received rapid HCV antibody testing, followed by venipuncture for RNA testing (antibody-positive only). Each enrollment question (yes/no) was compared with the testing results (positive/negative). RESULTS: Overall, 1892 people completed the questionnaire, including 621 (34%) who were currently on opioid agonist therapy (OAT); 30% of participants had been tested for HCV previously. About 71% had a history of drug use, of whom 13% had ever injected drugs; 52% had ever shared injecting equipment. The prevalence of HCV antibody and RNA was 6.9% (n = 130) and 4.8% (n = 90), respectively. The antibody prevalence was higher among people on OAT compared to those with no history of OAT (11.4% vs. 4.0%). History of drug use was the most accurate predictor of having a positive HCV antibody (sensitivity: 95.2%, negative predictive value: 98.9%) and RNA testing (sensitivity: 96.7%, negative predictive value: 99.5%). The sensitivity of the drug use question was lowest among people with no OAT history and new inmates (87% and 89%, respectively). Among all participants, sensitivity and negative predictive value of the other questions were low and ranged from 34 to 54% and 94 to 97%, respectively. CONCLUSIONS: In resource-limited settings, HCV screening based on having a history of drug use could replace universal screening in prisons to reduce costs. Developing tailored screening strategies together with further cost studies are crucial to address the current HCV epidemic in low- to middle-income countries.

10-Year Trends in Dietary Intakes in the High- and Low-Risk Areas for Esophageal Cancer: A Population-Based Ecological Study in Northern Iran.

BACKGROUND We assessed dietary intakes in the high- and low-risk areas for esophageal cancer (EC) in Golestan province, Northern Iran. METHODS Considering the EC rates, Golestan province was divided into high- and low-risk regions. Data on households' food consumption were obtained from the Statistical Center of Iran. We used multivariable logistic regression to assess the relationships between consumption of main food and EC risk. Adjusted odds ratios (aOR) were calculated. Joint point program was used for time trend analysis and average annual percent changes (AAPC) were reported. RESULTS Overall, 11910 households were recruited during 2006-2015. 4710 (39.5%) households were enrolled from the high-risk region. There were significant positive relationships between high consumption of sweets (aOR = 1.62; 95% CI: 1.24-2.10), oil/fat (aOR = 1.36; 95% CI: 1.04-1.79), and red meat (aOR = 1.33; 95% CI: 1.07-1.65) with EC risk. We found significant negative relationships between high consumption of dairy products (aOR = 0.62; 95% CI: 0.46-0.82), vegetables (aOR = 0.66; 95% CI: 0.50-0.87) and fruit (aOR = 0.72; 95% CI: 0.55-0.95) with the risk of EC. Time trend analysis showed a significant increasing trend in the proportions of households with low consumption of vegetables (AAPC = 4.71, p = 0.01) and dairy products (AAPC = 5.26, p = 0.02) in the low-risk region for EC. CONCLUSION Dietary intakes may be important etiological factors for EC in Northern Iran. Further studies are warranted to assess the role of dietary factors in this high-risk population.

Household Fuel Use and the Risk of Gastrointestinal Cancers: The Golestan Cohort Study.

BACKGROUND: Three billion people burn nonclean fuels for household purposes. Limited evidence suggests a link between household fuel use and gastrointestinal (GI) cancers. OBJECTIVES: We investigated the relationship between indoor burning of biomass, kerosene, and natural gas with the subsequent risk of GI cancers. METHODS: During the period 2004-2008, a total of 50,045 Iranian individuals 40-75 years of age were recruited to this prospective population-based cohort. Upon enrollment, validated data were collected on demographics, lifestyle, and exposures, including detailed data on lifetime household use of different fuels and stoves. The participants were followed through August 2018 with <1% loss. RESULTS: During the follow-up, 962 participants developed GI cancers. In comparison with using predominantly gas in the recent 20-y period, using predominantly biomass was associated with higher risks of esophageal [hazard ratio (HR): 1.89; 95% confidence interval (CI): 1.02, 3.50], and gastric HR: 1.83; 95% CI: 1.01, 3.31) cancers, whereas using predominantly kerosene was associated with higher risk of esophageal cancer (HR: 1.84; 95% CI: 1.10, 3.10). Lifetime duration of biomass burning for both cooking and house heating (exclusive biomass usage) using heating-stoves without chimney was associated with higher risk of GI cancers combined (10-y HR: 1.14; 95% CI: 1.07, 1.21), esophageal (10-y HR: 1.19; 95% CI: 1.08, 1.30), gastric (10-y HR: 1.11; 95% CI: 1.00, 1.23), and colon (10-y HR: 1.26; 95% CI: 1.03, 1.54) cancers. The risks of GI cancers combined, esophageal cancer, and gastric cancer were lower when biomass was burned using chimney-equipped heating-stoves (strata difference p-values=0.001, 0.003, and 0.094, respectively). Duration of exclusive kerosene burning using heating-stoves without chimney was associated with higher risk of GI cancers combined (10-y HR: 1.05; 95% CI: 1.00, 1.11), and esophageal cancer (10-y HR: 1.14; 95% CI: 1.04, 1.26). DISCUSSION: Household burning of biomass or kerosene, especially without a chimney, was associated with higher risk of some digestive cancers. Using chimney-equipped stoves and replacing these fuels with natural gas may be useful interventions to reduce the burden of GI cancers worldwide. https://doi.org/10.1289/EHP5907.

Trends in the Incidence of Stomach Cancer in Golestan Province, a High-risk Area in Northern Iran, 2004-2016.

BACKGROUND: We aimed to present the temporal and geographical trends in the incidence of stomach cancer in the Golestan province, a high-risk area in Northern Iran. METHODS: This study was conducted on stomach cancer cases registered in the Golestan Population-based Cancer Registry (GPCR) during 2004-2016. Age-standardized incidence rates (ASRs) per 100000 person-years were calculated. The Joinpoint regression analysis was used to calculate the average annual percent changes (AAPC). We also calculated the contribution of population aging, population size and risk to the overall changes in incidence rates. RESULTS: Overall, 2964 stomach cancer patients were registered. The ASR of stomach cancer was significantly higher in men (26.9) than women (12.2) (P<0.01). There was a significant decreasing trend in incidence of stomach cancer in men (AAPC=-1.80, 95% CI: -3.30 to-0.28; P=0.02). We found a higher ASR of stomach cancer in the rural (21.4) than urban (18.1) (P=0.04) population, as well as a significant decreasing trend in its rates (AAPC=-2.14, 95% CI: -3.10to-1.17; P<0.01). The number of new cases of stomach cancer increased by 22.33% (from 215 in 2004 to 263 in 2016), of which 18.1%, 25.1% and -20.9% were due to population size, population aging and risk, respectively. Our findings suggest a higher rate for stomach cancer in eastern areas. CONCLUSION: We found high incidence rates as well as temporal and geographical diversities in ASR of stomach cancer in Golestan, Iran. Our results showed an increase in the number of new cases, mainly due to population size and aging. Further studies are warranted to determine the risk factors of this cancer in this high-risk population.

Letter to the editor: efficacy of different methods of combination regimen administrations including dexamethasone, intravenous immunoglobulin, and interferon-beta to treat critically ill COVID-19 patients: a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: There is little information about Coronavirus Disease 2019 (COVID-19) management for critically ill patients. Most of these patients develop acute respiratory distress syndrome (ARDS) due to excessive inflammatory response and the ensuing cytokine storm. Anti-inflammatory drugs including corticosteroids can be used to effectively reduce the effect of this cytokine storm and lung damage. However, corticosteroids can have side effects, so simultaneous administration of immunoglobulin (IV-IG) and interferon-beta can help manage treatment using corticosteroids. Therefore, we designed a trial to test our hypothesis that early administration of dexamethasone in combination with IV-IG and interferon-beta can reduce the effect of the cytokine storm in critically ill patients COVID-19. TRIAL DESIGN: A phase two multi-center randomized controlled trial (RCT) with three parallel arms (1:1:1 ratio). PARTICIPANTS: They will be hospitalized patients with severe COVID-19 who have positive RT-PCR test and have blood oxygen saturation levels (SpO2) less than 90% and respiratory rate higher than 24 per minute or have involvement of more than 50% of their lung when viewed using computed tomography (CT)-scan. The age range of patients will be 18-70 years old. EXCLUSION CRITERIA: the need for intubation; allergy, intolerance, or contraindication to any study drug including dexamethasone, IV-IG, and interferon-beta; pregnancy or lactation; known HIV positive or active hepatitis B or C. The study will be conducted in several hospitals of the Golestan province, Iran. INTERVENTION AND COMPARATOR: The study subjects will be randomly allocated to three treatment arms: two experimental groups (two arms: Intervention 1 and Intervention 2) and one Control Group, which will be matched for age and sex using frequency matching method. Each eligible patient in the control arm will receive the standard treatment for COVID-19 based on WHO guidelines and the Ministry of the Health and Medical Education (MOHME) of Iran. Each patient in the Intervention Group 1 will receive the standard treatment for COVID-19 and dexamethasone, at the first 24 hours' time of admission. The intervention begins with the administration of dexamethasone based on the SpO2 levels. If the level of SpO2 does not improve after 24 hours, IV-IG (400 mg/kg once daily for 5 days) and interferon-beta (7 doses every other day) will be prescribed along with dexamethasone administration. In Intervention Group 2, the administration of dexamethasone will be started within the first 24 hours' time of admission and will be continued for 48-72 hours and then the SpO2 level will be checked. Then, if the level of SpO2 has not improved after that time, IV-IG and interferon-beta will be prescribed as the same dosage as Group 1. If the percentages of the SpO2 level are between 85 and 90/ 80 and 85/ 75 and 80/ less than 75, the dosages will be 4 mg every 12 hours/ 4 mg every 8 hours/ 8 mg every 12 hours/ 8 mg every 8 hours, respectively. According to the WHO recommendation, all participants will have the best available supportive care with full monitoring. MAIN OUTCOMES: Primary: An increase in the SpO2 level to reach more than 90% in each case, which will be assessed by the oximeter. Secondary: The duration of hospital stays; intubation status and the percentage of patients who are free of mechanical ventilation; the mortality rates during hospitalization and one month after the admission time. RANDOMISATION: Participants will be allocated into either control or intervention groups with a 1:1:1 allocation ratio using a computer random number generator to generate a table of random numbers for simple randomization. BLINDING (MASKING): The project's principal investigator (PI) is unblinded. However, the PI will not analyse the data and interpret the results. An unblinded researcher (a pharmacist) will cover the drug's bottles with aluminium foil and prepare them interventions and control drugs in a syringe with a code so that patients are blinded. This person will have no patients contact. The staff and nurses, caring for the patients, will be unblinded for each study group due to the nature of this study. The staff that take outcome measurements will be blinded. The laboratory technicians will also be blinded as well as the statistical team. These study statisticians will have access to coded data and will analyse the data labelled as group X, group Y, and group Z. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size will be 105 critically ill COVID-19 patients, who will be allocated randomly to the three trial arms with 35 patients in each group. TRIAL STATUS: Recruitment is ongoing. The study began on April 18 2020 and will be completed June 19 2020. This summary describes protocol version 1; April 2 2020. TRIAL REGISTRATION: https://www.irct.ir/. Identifier: IRCT20120225009124N4 version 1; Registration date: April 2 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The full protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.