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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.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.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.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.

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.

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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). © 2021 Academy of Medical Sciences of I.R. Iran. All rights reserved.

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.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.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).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.

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.

Mesenchymal stem cells (MSCs), one of the most important stromal cells in the tumor microenvironment, play a major role in the immunomodulation and development of tumors. In contrast to immunomodulatory effects of bone marrow-derived MSCs, resident MSCs were not well studied in tumor. The aim of this study was to compare the immunomodulatory properties and protein secretion profiles of MSCs isolated from breast tumor (T-MSC) and normal breast adipose tissue (N-MSC). T-MSCs and N-MSCs were isolated by the explant culture method and characterized, and their immunomodulatory function was assessed on peripheral blood lymphocytes (PBLs) by evaluating the effects of MSC conditioned media on the proliferation and induction of some cytokines and regulatory T cells (Tregs) by BrdU assay, ELISA, and flow cytometry. In addition, we compared the secretion of indoleamine 2,3-dioxygenase (IDO), vascular endothelial growth factor (VEGF), matrix metallopeptidase (MMP)-2, MMP-9, and Galectin-1. T-MSCs showed a higher secretion of transforming growth factor beta (TGF-β), prostaglandin E2 (PGE2), IDO, and VEGF and lower secretion of MMP-2 and MMP-9 compared with N-MSCs. However, no significant difference was found in the secretion of interferon gamma (IFN-γ), interleukin 10 (IL10), IL4, IL17, and Galectin-1 in T-MSCs and N-MSCs. The immunomodulatory effect of soluble factors on PBLs showed that T-MSCs, in contrast to N-MSCs, stimulate PBL proliferation. Importantly, the ability of T-MSCs to induce IL10, TGF-β, IFN-γ, and PGE2 was higher than that of N-MSCs. In addition, T-MSCs and N-MSCs exhibited no significant difference in Treg induction. MSCs educated in stage II breast cancer and normal breast adipose tissue, although sharing a similar morphology and immunophenotype, exhibited a clearly different profile in some immunomodulatory functions and protein secretions.

Summary Background A fixed-dose combination therapy (polypill strategy) has been proposed as an approach to reduce the burden of cardiovascular disease, especially in low-income and middle-income countries (LMICs). The PolyIran study aimed to assess the effectiveness and safety of a four-component polypill including aspirin, atorvastatin, hydrochlorothiazide, and either enalapril or valsartan for primary and secondary prevention of cardiovascular disease. Methods The PolyIran study was a two-group, pragmatic, cluster-randomised trial nested within the Golestan Cohort Study (GCS), a cohort study with 50 045 participants aged 40–75 years from the Golestan province in Iran. Clusters (villages) were randomly allocated (1:1) to either a package of non-pharmacological preventive interventions alone (minimal care group) or together with a once-daily polypill tablet (polypill group). Randomisation was stratified by three districts (Gonbad, Aq-Qala, and Kalaleh), with the village as the unit of randomisation. We used a balanced randomisation algorithm, considering block sizes of 20 and balancing for cluster size or natural log of the cluster size (depending on the skewness within strata). Randomisation was done at a fixed point in time (Jan 18, 2011) by statisticians at the University of Birmingham (Birmingham, UK), independent of the local study team. The non-pharmacological preventive interventions (including educational training about healthy lifestyle—eg, healthy diet with low salt, sugar, and fat content, exercise, weight control, and abstinence from smoking and opium) were delivered by the PolyIran field visit team at months 3 and 6, and then every 6 months thereafter. Two formulations of polypill tablet were used in this study. Participants were first prescribed polypill one (hydrochlorothiazide 12·5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg). Participants who developed cough during follow-up were switched by a trained study physician to polypill two, which included valsartan 40 mg instead of enalapril 5 mg. Participants were followed up for 60 months. The primary outcome—occurrence of major cardiovascular events (including hospitalisation for acute coronary syndrome, fatal myocardial infarction, sudden death, heart failure, coronary artery revascularisation procedures, and non-fatal and fatal stroke)—was centrally assessed by the GCS follow-up team, who were masked to allocation status. We did intention-to-treat analyses by including all participants who met eligibility criteria in the two study groups. The trial was registered with ClinicalTrials.gov , number NCT01271985 . Findings Between Feb 22, 2011, and April 15, 2013, we enrolled 6838 individuals into the study—3417 (in 116 clusters) in the minimal care group and 3421 (in 120 clusters) in the polypill group. 1761 (51·5%) of 3421 participants in the polypill group were women, as were 1679 (49·1%) of 3417 participants in the minimal care group. Median adherence to polypill tablets was 80·5% (IQR 48·5–92·2). During follow-up, 301 (8·8%) of 3417 participants in the minimal care group had major cardiovascular events compared with 202 (5·9%) of 3421 participants in the polypill group (adjusted hazard ratio [HR] 0·66, 95% CI 0·55–0·80). We found no statistically significant interaction with the presence (HR 0·61, 95% CI 0·49–0·75) or absence of pre-existing cardiovascular disease (0·80; 0·51–1·12; pinteraction=0·19). When restricted to participants in the polypill group with high adherence, the reduction in the risk of major cardiovascular events was even greater compared with the minimal care group (adjusted HR 0·43, 95% CI 0·33–0·55). The frequency of adverse events was similar between the two study groups. 21 intracranial haemorrhages were reported during the 5 years of follow-up—ten participants in the polypill group and 11 participants in the minimal care group. There were 13 physician-confirmed diagnoses of upper gastrointestinal bleeding in the polypill group and nine in the minimal care group. Interpretation Use of polypill was effective in preventing major cardiovascular events. Medication adherence was high and adverse event numbers were low. The polypill strategy could be considered as an additional effective component in controlling cardiovascular diseases, especially in LMICs. Funding Tehran University of Medical Sciences, Barakat Foundation, and Alborz Darou.

Esophageal squamous cell carcinoma (ESCC) shows a remarkable variation in incidence which 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. The mutational profiles of ESCC 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 the differences in ESCC incidence. APOBEC associated mutational signatures SBS2 and SBS13 were present in 88% and 91% of cases respectively and accounted for a quarter of the mutation burden on average, indicating that activation of APOBEC is a crucial step in ESCC tumor development.

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. .

Summary 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.

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.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.Significant up-regulation of ARSD was observed in tumor tissues in comparison with its antisense (p0.05). 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 (p0.05). 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.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.

Background: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia and risk factors associated for mortality. Methods: In this retrospective cohort study, we included inpatient with acute respiratory distress syndrome at Golestan University of Medical Sciences Hospitals (Golestan province, Iran) who had been discharged or had died in 2020. Epidemiological, clinical, and laboratory data, including samples for viral RNA detection, 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: In overall 2,835 acute respiratory distress syndrome patients were included in this study, of these patients, 874 (30.83.9%) were positive for 2019­nCoV, and 1,046 (36.90%) were negative and 915 (32.28%) were not available for PCR result. Five hundred and sixty-three patients (19.86%) died, 1,687 patients (59.51%) were recovered, and 585 (20.63%) under treatment. 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 (SpO2Conclusions: The 2019-nCoV infection caused collections of severe respiratory illness and was associated high ratio of hospitalization in ICU and high mortality. Older age and comorbidities were associated with more risk of death among patients with 2019­nCoV.

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.

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.

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.

BackgroundHepatitis 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.MethodsBetween 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).ResultsOverall, 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.ConclusionsIn 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.

Summary: Background: Evidence is emerging for a role of opiates in various cancers. In this study, we aimed to investigate the association between regular opium use and cancer incidence. Methods: This study was done in a population-based cohort of 50 045 individuals aged 40–75 years from northeast Iran. Data on participant demographics, diet, lifestyle, opium use, and different exposures were collected upon enrolment using validated questionnaires. We used proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% CIs for the association between opium use and different cancer types. Findings: During a median 10 years of follow-up, 1833 participants were diagnosed with cancer. Use of opium was associated with an increased risk of developing all cancers combined (HR 1·40, 95% CI 1·24–1·58), gastrointestinal cancers (1·31, 1·11–1·55), and respiratory cancers (2·28, 1·58–3·30) in a dose-dependent manner (ptrend

Background: Since December 2019, the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has challenged the world. In this descriptive study, we aim to share the clinical information of 427 Iranian COVID-19 patients. Methods: The different information on COVID-19 patients who were hospitalized from 24 February 2020 to 1 April 2020 was analyzed using R software. The patients were categorized into two groups as non-severe or severe and survivor or non-survivor cases. Outcomes of the cases were followed up until one month after the time of admission. Findings: Overall, the median age of the patients was 53 with a difference of ten years between two categories in each group. Among patients, 50·8% were males who had worse outcomes than female patients. Cough (72·8%), fever (69·3%), and dyspnea (64·0%) were the most common symptoms. There were more underlying comorbidities in the group of severe (73·5%) and non-survivor (77·5%) cases compared to the non-severe (53·6%) and survivor (44·1%) groups. Changes in the pattern of the parameters of complete blood counts including lymphopenia (227/333; 68·2%) were the most prominent findings. Factors associated with the liver and kidney damage were significantly increased in patients, especially in non-survivor cases. Around 90% of the COVID-19 patients had at least one abnormality in the chest CT scans including simultaneously both crazy paving and consolidation patterns (27·1%), followed by the ground-glass opacity (24·7%). Interpretation: According to the results, the patients' age, underlying comorbidities, percentage of SpO2, and blood laboratory findings at the time of admission may indicate the progression of the disease in the coming days. Funding Statement: The Golestan University of Medical of Sciences, Iran. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The ethics committee of Golestan University of Medical Sciences approved the study (IR.GOUMS.REC.1398.383).

Introduction: Pheochromocytoma is a rare catecholamine-secreting tumor with gastrointestinal manifestations. Case description: Herein, we report a 50 years old female patient with abdominal pain, altered bowel habit, abdominal mass lesion and laboratory features of pheochromocytoma. The patient was admitted with abdominal pain, back pain, arthralgia, weakness, lethargy, cold sweat and weight loss. She had history of diabetes mellitus, ischemic heart disease and hyperlipidemia. On admission, she was normotensive and had normal physical examination. Upper and lower endoscopies were normal. Transabdominal sonography and CT scan showed large heterogeneous masses with central necrosis and calcification in adrenal regions. In addition, 24-hour urine evaluation showed elevated vanillylmandelic acid, metanephrine and normetanephrine levels. She underwent bilateral adrenalectomy. Pathologic evaluation showed typical characteristics of pheochromocytoma. Conclusions: In any patient with abdominal pain and abdominal mass, low threshold for diagnosis of rare but often lethal pheochromocytoma is suggested. KEYWORDS: pheochromocytoma, constipation, abdominal pain

Adrenal gland cysts are rare indications of adrenal diseases, which are commonly asymptomatic. In radiological studies, these cysts, known as incidentalomas, are often detected by coincidence accounting for 6% of the population. Adrenal incidentalomas are commonly detected, and autonomous cortisol hypersecretion is the most prevalent abnormality associated with these masses. Since this complication is recurrent, it requires intermittent morphological and hormonal evaluation for several years. In this paper, we aimed to present the case of a 52-year-old woman with complaints of vague abdominal pain. After laparotomy, the tumor was removed, and umbilical herniorrhaphy was performed on the patient. Laparoscopic adrenalectomy is the first-line surgical treatment for this type of incidentaloma. Ultrasonography revealed an echogenic mass (diameter: 4 cm) in the left adrenal gland of the patient, which was not associated with hernia. In addition, CT-scan showed that the adrenal lesion was hypodense and heterogeneous (diameters: 81*53 mm) with sharp, irregular borders.

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) (PP=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; PConclusion: 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.

We aimed to present the time trends and geographical distribution of lung cancer in Golestan province, a high-risk area for pulmonary tuberculosis (TB) in Northern Iran (2004-2016).Data on incident primary lung cancers were obtained from the Golestan population-based cancer registry. The data were analyzed by CanReg-5 software to calculate the age-standardized incidence rates (ASRs). We used Joinpoint software for time trend analysis. Average annual percent changes were calculated. The contribution of population aging, population growth and risk to the overall changes in incidence of lung cancer were determined using partitioning analysis.Overall, 1829 cases of lung cancer were registered by the GPCR during 2004-2016, of which 1274 (69.7%, ASR in 2016 = 21.3) were men and 555 (30.3%, ASR in 2016 = 11.4) were women. The results of Joinpoint regression suggested a significant increasing trend in incidence of lung cancer in Golestan province during 2004 and 2016 (AAPC = 3.74; p-value = 0.01) with more prominent increasing in rural population (AAPC = 4.93; p-value0.01). The number of new cases of lung cancer increased by 131.6% (from 98 in 2004 to 227 in 2016), of which 34.1%, 22.3% and 75.3% were due to population size, population aging and risk, respectively. Hot points of lung cancer were found in western parts of the Golestan.With high incidence rates and increasing trends of lung cancer, further studies are warranted to clarify the role of TB and other risk factors on its burden in this population.

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.

Brain and other central nervous system (CNS) tumors represent almost 3% of all new cancer cases worldwide and comprise a heterogeneous group of tumors with varying epidemiologic and clinical characteristics. The aim of this study is to present the distribution and trends in brain and other CNS cancer incidence in Golestan, Iran during a 10-year period.Data on primary brain and other CNS cancers diagnosed between 2004 and 2013 were obtained from the Golestan population-based cancer registry (GPCR) dataset. We computed age-standardized incidence rates (ASRs) per 100000 personyears. In order to assess changes in incidence over time, we calculated the estimated annual percentage change (EAPC) and corresponding 95% confidence intervals (CIs) to detect significant trends.Over the 10-year period (2004-2013), the incidence of brain and other CNS cancer was observed to increase for all ages (EAPC: 1.13, 95% CI: -6.06, 8.87). After 2008, the trends appear to have stabilized. Incidence rates were higher in males than females (ratio: 1.2) and glioblastoma was the most common tumor subtype (15.1% of all malignant tumors).Trends and patterns in the burden of brain and other CNS cancer require careful monitoring alongside future research to increase our understanding of potential risk factors.

There is currently little known about the epidemiology of lymphomas in Iran. The aim of this paper is to describe the geographic and time variations in incidence rates of lymphomas in the Golestan province between 2004 and 2013.The Golestan Population-based Cancer Registry (GPCR) routinely registers primary cancer patients from all sources (e.g. pathology centers, hospitals, etc.) throughout the Golestan province. We obtained data on newly-diagnosed lymphomas in Golestan during 2004-2013 from the GPCR dataset. Crude rates and age standardized incidence (ASR) rates (per 100000) of lymphomas were estimated, joinpoint regression was used to quantify incidence trends and average annual percent changes (AAPCs) were calculated.In total, 898 new cases of lymphoma were registered in the GPCR during 2004-2013. The ASR of Hodgkin lymphoma (HL) was 1.5 and 1.1 in males and females, respectively, while corresponding non-Hodgkin lymphoma (NHL) rates were greater, at 6.5 and 3.4 in males and females, respectively. Our results indicated a significant difference in the trends of HL between males (AAPC = -3.2) and females (AAPC = 3.6, P value = 0.001). The incidence rates of lymphoma were considerably higher in the urban population (ASR = 7.3) compared to those residing in rural areas (ASR = 5.3, P value = 0.054). We also found higher incidence rates for both HL and NHL in the western parts of the Golestan province.The incidence rates of lymphoma in the Golestan province are relatively high and vary geographically, with a higher incidence observed in the western area. Such differences may reflect unknown lifestyle and environmental determinants linked to ethnic susceptibility differing between the two areas.

Background: A fixed-dose combination therapy ("polypill" strategy) has been proposed as an approach to reduce the burden of cardiovascular disease (CVD), especially in lower resource settings. We conducted the PolyIran Study to assess the effectiveness and safety of a four-component polypill including aspirin, atorvastatin, hydrochlorothiazide and either enalapril or valsartan, for primary and secondary prevention of CVD. Methods: The study population comprised of rural participants of the Golestan Cohort Study aged 50 years or older. Considering villages as clusters, the study participants were cluster randomized to a package of non-pharmacological preventive interventions either alone (minimal care arm) or together with a once daily polypill (polypill arm). Participants were followed for 60 months. The primary outcome was occurrence of major cardiovascular events (MCVE), which was compared between the two arms using Cox regression models with shared frailty. Findings: Overall, 6838 individuals were enrolled in the study, including 3417 (in 116 clusters) in the minimal care arm and 3421 (in 120 clusters) in the polypill arm. Median (interquartile range) adherence to polypill tablets was 80.5% (48.5%-92.2%). During the follow up, 202 and 301 participants in the polypill and minimal care arms, respectively, had one or more MCVE (adjusted hazard ratio [HR]=0.66; 95% confidence interval [CI]: 0.55-0.80). Polypill was effective for both primary and secondary prevention of CVD. When restricted to participants with high adherence, the risk of MCVE was further reduced (adjusted HR=0.43; 95%CI: 0.33-0.55). Overall, the frequency of adverse events was comparable between the two arms. Interpretation: Using polypill was effective in preventing MCVE. Medication adherence was high, and rates of adverse events were low. The polypill strategy may be considered as an additional effective component in controlling CVDs, especially in low resources settings. Trial Registration: Cllinicaltrials.gov identifier: NCT01271985. Funding Statement: The study was supported by and Alborz Darou, Barakat Foundation, and Tehran University of Medical Sciences. Golestan Cohort study was supported by Cancer Research UK (grant number: C20/A5860), Tehran University of Medical Sciences (grant number: 81/15), and the International Agency for Research on Cancer. Declaration of Interests: The authors disclose no conflicts. Ethics Approval Statement: The protocol of the PolyIran Study was reviewed and approved by Institutional Review Board (IRB) of Digestive Diseases Research Institute and Tehran University of Medical Sciences.

Background We examine recent trends in the major cancers occurring in the Golestan province, a high-risk region for upper gastrointestinal cancers in Northern Iran, and provide short-term cancer predictions of the future cancer burden. Methods New cancer cases diagnosed in Golestan 2004–2016 were obtained from the Golestan population-based cancer registry (GPCR) database, and age-standardized rates by cancer site, year and sex calculated per 100,000 person-years. Using IARC’s DepPred package we fitted time-linear age-period models to the available GPCR data to predict the cancer incidence burden in the year 2025. We calculated the contribution of demographic changes versus changes in risk to the overall changes in incidence from 2016 to 2025. Results The number of new cancer cases (excluding non-melanoma skin cancers) in 2025 is predicted to increase by 61.3% from 2678 cases in 2016 to 4319 cases. While a 17.6% reduction in the number of esophageal cancer cases is predicted by 2025, the number of new cases for each of the remaining major cancers is predicted to increase over the next decade, including cancers of the stomach (a 36.1% increase from 2016 to 2025), colorectum (56.2%), lung (67.8%), female breast (93.2%), prostate (101.8%) and leukemia (96.1%). The changes in the population structure and risk contributed 37.8% and 23.5% respectively, to the overall increase in incidence. Conclusion Other than for the major upper gastrointestinal cancer types, the incidence rates of common cancers observed in the province are on the rise, reinforcing the need for continuous surveillance, as well as the design and implementation of effective cancer control programs.

Golestan province, in Northern Iran, is a high-risk area for esophageal squamous cell carcinoma (SCC). SCC is also the most common histological type of cancers of the head and neck region including cancers of oral cavity, oropharynx, hypopharynx and larynx. We aimed to present the incidence rate of head and neck SCC (HNSCC) in Golestan province during 2004 and 2013.Data on HNSCC were obtained from Golestan population-based cancer registry (GPCR). Quality control and data analysis were performed using CanReg software. Age standardized incidence rates (ASRs) were calculated using the world standard population. The ASRs were presented per 100000 person-years for different genders, residence places and years.During the 10-year period from 2004-2013, 434 cases of HNSCC were registered. 327 (75.3%) of these cases were male, 51.2% (222 cases) lived in urban areas and 351 (80.9%) of the total HNSCCs occurred in the larynx. Overall, the ASR of HNSCCs in Golestan province was 4.8. The ASR of HNSCCs was more than two-fold higher in male (6.6) than female (3.0). Our results showed an increasing trend in ASR of larynx cancer during the study period both in male and female.We found relatively high rates of larynx cancer in Golestan province. Our results also showed higher rates of HNSCC in males and urban population. Considering common risk factors between HNSCCs and esophageal cancer, further studies are needed to clarify different aspects of HNSCCs (including epidemiology and risk factors) in this high-risk population.

Introduction The Golestan population-based cancer registry (GPCR) was established in Golestan province, Northern Iran, within the Asian belt with predominance of upper-gastrointestinal cancers. We aimed to present the experiences of the registry in a resource–limited setting over the 10 years since its inception (2004–2013). Methods The GPCR was established as a research project to enable sustainable funding. A clear plan was developed for use of the GPCR data. New primary cancers were registered based on international standards, indices of data quality were routinely assessed and age-standardized incidence rates (ASR) per 100,000 person-years calculated using IARC’s CanReg-5 software. Results Overall, 19807 new cancer cases were registered during the study period, an average of 1981 cases per annum, with overall ASR of 175.0 and 142.4 in males and females, respectively. The GPCR data suggested gastrointestinal and breast cancers as the most common malignancies in Golestan province. We observed increasing incidence rates of breast and colorectal cancers but declining trends of esophageal cancer. Overall, indices of data quality were within acceptable ranges. Conclusions The GPCR data have been included in IARC’s Cancer Incidence in Five Continents series, were used in 21 research projects, and published as 30 research papers. The key ingredients for the successful establishment and maintenance of the GPCR included sustainable sources of funding, a clear action plan for the use of data as well as stakeholder cooperation across all areas of the registration. The GPCR may be considered as a model for planning population-based cancer registries in lesser-resourced settings.

Background: Malignancies of the female reproductive tract are estimated to be the third most common group of cancers in women. Objectives: We here aimed to present their epidemiological features in Golestan province located in Northeast of Iran. Materials and Methods: Data on primary female reproductive cancers diagnosed between 2004-2010 were obtained from Golestan Population-based Cancer Registry (GPCR). CanReg-4 and SPSS software were used for data entry and analysis. Age standardized incidence rates (ASR) (per 100,000 person-years) were calculated using the world standard population. Poisson regression analysis was used to compare incidence rates. P-values of less than 0.05 were considered as significant. Results: A total of 6,064 cancer cases were registered in Golestan females in the GPCR during 2004-2010, of which 652 cases (11%) were female reproductive cancers. Cancers of the ovary (ASR=6.03) and cervix (ASR=4.97) were the most common. We found significant higher rates in females living in cities than in villages. Our results showed a rapid increase in age specific incidence rates of female reproductive cancers at the age of 30 years. Conclusions: We found significant higher rates of female reproductive cancers among residents of cities than villages. Differences in the prevalence of risk factors including reproductive behavior between the two populations may partly explain such diversity. Our results also showed a rapid increase in incidence rates of these cancers in young age females. Further studies are warranted to determine risk factors of female reproductive cancers in our population.

It is the practice of many surgeons to use the routine nasogastric tube after biliary operations, but its usefulness has been questioned. This study was designed to determine the effect of postoperative nasogastric intubation on gastrointestinal function in patients with obstructive jaundice. In this randomized clinical trial, 40 patients who underwent choledochoduodenostomy or hepaticojejunostomy were randomly divided into two groups. Patients in the experimental group did not have the nasogastric tube, and in the control group the nasogastric tube was routinely applied after surgery. Gastrointestinal function was compared in these two groups. Patients with no nasogastric intubation did not show any postoperative complications or prolonged hospital stay. On the contrary, nasogastric tube insertion postponed return of bowel function and increased the incidence of nausea and vomiting, while it did not affect the incidence of postoperative ileus. Routine use of the nasogastric tube after choledochoduodenostomy or hepaticojejunostomy can delay normal gastrointestinal function and increase postoperative discomfort.

Gossypiboma is derived from two Latin and Swahili words including gossypium (cotton) and boma [place of concealment] (1). It is a kind of retained foreign body (RFB) following surgery (2). It causes two types of reaction including exudative inflammatory reaction and aseptic fibrotic reaction. The first type causes reaction to the material of sponge and presents as a mass in the body. The second forms an abscess and results in early diagnosis, leading to surgical removal (3).