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1.  Opium and bladder cancer: A systematic review and meta-analysis of the odds ratios for opium use and the risk of bladder cancer 
PLoS ONE  2017;12(6):e0178527.
Objective
The association between opium use and bladder cancer has been investigated in many studies, with varying reporting results reported. This study aims to estimate the total odds ratio for the association between bladder cancer and opium consumption using meta-analysis.
Methods
The study was designed according to PRISMA guidelines. Two independent researchers searched for the relevant studies using PubMed, Web of Science, Scopus, OVID, Embase, and Google Scholar. After systematic screening of the studies identified during the first step, Cochrane risk of bias tool was determined for the selected studies. The case-control and the cohort studies were investigated to assess risk of bladder cancer due to opium use. In addition, the cross-sectional studies were analysed separately to assess frequency of opium consumption. These estimates were combined using the inverse variance method. Fixed or random effect models were applied to combine the point odds ratios. The heterogeneity between the primary results was assessed using the Cochran test and I-square index. The suspected factors for heterogeneity were investigated using meta-regression models. An Egger test was conducted to identify any probable publication bias. Forest plots illustrated the point and pooled estimates. All analyses were performed using Stata version 14 software and RevMan version 5.3.
Results
We included 17 primary studies (11 case-control, one cohort and five cross-sectional) in the final meta-analysis. The total odds ratios (95% confidence intervals) for developing bladder cancer by opium use alone, and concurrent use of opium and cigarettes were estimated as 3.85 (3.05–4.87) and 5.7 (1.9–16.3) respectively. The odds ratio (95% confidence interval) for opium use with or without cigarette smoking was estimated as 5.3 (3.6–7.7).
Conclusion
This meta-analysis showed that opium use similar to cigarette smoking and maybe with similar mechanisms can be a risk factor for bladder cancer. It is therefore expected to be a risk factor for other cancers.
doi:10.1371/journal.pone.0178527
PMCID: PMC5460843  PMID: 28586371
2.  The Relationship of Opium Addiction with Coronary Artery Disease 
Objectives:
There is some controversy regarding the effect of opium addiction on the coronary artery disease (CAD). The aim of this study was to determine the association between chronic opium consumption and CAD.
Methods:
This study had a case-control design. The patients recruited to the study were selected from angiography files in Department of Cardiology in Kerman University of Medical Sciences, Kerman, Iran. The comparison was done between CAD patients and normal subjects. Opium addiction was diagnosed by patient self-report and confirmed with interview based on DSM-IV criteria. Odds ratio with 95% confidence interval were estimated by unconditional logistic regression.
Results:
The risk factor of CAD was the same in the two study groups. The significant difference in opium consumption was demonstrated between CAD patients and normal coronary artery subjects (OR=3.8, 95%CI=1.5-9.5). Because of the strong association between cigarette smoking and opium addiction, analysis was done in smoker and non-smoker groups separately. Logistic regression showed opium addiction was the independent risk factor for CAD in non-smokers after adjusting to other CAD risk factors (OR=38, 95%CI=2.7-531.7), but in cigarette smokers opium was not a significant risk factor (OR=13.2, 95%CI=0.85-206.5).
Conclusions:
We confirmed that the opium was an independent risk factor for CAD. Health managers and policy makers should try to aware general population and prepare many preventive programs against substance abuse.
PMCID: PMC3075529  PMID: 21566789
Opium; Coronary artery disease; Angiography; Risk factor
3.  Is opium addiction a risk factor for ischemic heart disease and ischemic stroke? 
Background:
The main source of studies about effects of opium consumption on heart and brain attacks originates from Iran Therefore the aim of the present study was to assess opium addiction as a probable influencing factor for ischemic heart disease and ischemic stroke.
Materials and Methods:
A cross-sectional study was carried out in two Cardiology and Neurology clinics in Eastern Iran in 2011. Diagnosis of Ischemic Heart Disease (IHD) and Ischemic Stroke (IS) was made by Cardiologist and Stroke Neurologist respectively. The influence of gender, hypertension, diabetes, hyperlipidemia, cigarette smoking, oral and inhaled opium consumption on distribution of IHD and IS were evaluated.
Results:
Five hundred fifty eight patients (307 females, 251 males) with mean age 56.2 years enrolled the study. On adjusted odds ratios of our whole 558 patients, only hypertension and diabetes had a significant influence on occurrence of IHD; (P = 0.000 and P = 0.000) respectively. Oral and inhaled routes of opium addiction did not have a significant effect on occurrence of IHD; [OR = 1.172, 95% CI = 0.624–2.203, P = 0.621] and [OR = 1.820, 95% CI = 0.811–4.085, P = 0.147] respectively. Hypertension and diabetes were significant risk factors of IS in our 558 patients at multivariate analysis; (P = 0.000, P = 0.020). Oral opium addiction was as significant protective factor of IS in our study group; OR = 0.211, 95% CI = 0.079–0.564, P = 0.002, while inhaled opium addiction did not have a significant effect on occurrence of IS in our patients at; OR = 1.760, 95% CI = 0.760–4.076, P = 0.187.
Conclusion:
Oral opium consumption is a protective factor of IS but not IHD. Inhaled opium addiction does not have a significant influence on occurrence of IS and IHD.
PMCID: PMC3698656  PMID: 23825997
Addiction; heart; ischemic; opium; stroke
4.  Opium addiction and severity of coronary artery disease: a case-control study 
BACKGROUND:
Coronary artery disease (CAD) is a leading cause of morbidity and mortality in the world. Determination of the risk factors and high risk groups plays an important role in the prevention and controlling programs. The present study aims to determine the relationship between opium consumption and severity of CAD.
METHODS:
In this hospital based case-control study, 299 patients who were candidates for coronary angiography from 2006 to 2007 were recruited. The patients’ history of opium addiction was taken. Based on their history, they were categorized into three groups: non users, occasional users and current users. The relationship between opium addiction and severity of CAD was analyzed by a multiple logistic regression model, STATA v.10.
RESULTS:
According to angiographic data, patients were divided into 3 groups: 84 patients (28.09%) as non coronary artery disease, 81 patients (27.09%) as mild CAD and the remaining 134 patients (44.82%) as severe CAD. Univariate analysis showed that current opium users had higher odds of severe CAD compared with non users. Multivariate analysis showed a significant relationship between age, diabetes, hyperlipidemia, gender and severity of coronary artery stenosis.
CONCLUSIONS:
The findings indicated that current opium users - in comparison with non users - have a higher risk for severe CAD. But it is roughly confounded by other co-factors such as cigarette smoking, age and sex. A dose-response was noticed between the type of opium consumption and the severity of CAD.
PMCID: PMC3082781  PMID: 21526055
Coronary Artery Disease; Atherosclerosis; Opium; Risk Factor
5.  Opium use, cigarette smoking, and alcohol consumption in relation to pancreatic cancer 
Medicine  2016;95(28):e3922.
Supplemental Digital Content is available in the text
Abstract
Background and Aims:
Although several studies have suggested opium as a risk factor for cancers of the esophagus, stomach, larynx, lung, and bladder, no previous study has examined the association of opium with pancreatic cancer. We aimed to study the association between opium use and risk of pancreatic cancer in Iran, using a case-control design. We also studied the association of cigarette smoking and alcohol consumption with pancreatic cancer, for which little information was available from this population.
Methods:
Cases and controls were selected from patients who were referred to 4 endoscopic ultrasound centers in Tehran, Iran. We recruited 316 histopathologically (all adenocarcinoma) and 41 clinically diagnosed incident cases of pancreatic cancer, as well as 328 controls from those with a normal pancreas in enodosonography from January 2011 to January 2015. We used logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
Results:
After adjustment for potential confounders, opium use (OR 1.91; 95% CI 1.06–3.43) and alcohol consumption (OR 4.16; 95% CI 1.86–9.31) were significantly associated with an increased risk of pancreatic cancer. We did not find an association between ever tobacco smoking and pancreatic cancer risk (OR 0.93; 95% CI 0.62–1.39).
Conclusion:
In our study, opium use and alcohol consumption were associated with an increased risk of pancreatic cancer, whereas cigarette smoking was not.
doi:10.1097/MD.0000000000003922
PMCID: PMC4956779  PMID: 27428185
alcohol; opium; pancreatic cancer; tobacco
6.  Association between opium use and metabolic syndrome among an urban population in Southern Iran: Results of the Kerman Coronary Artery Disease Risk Factor Study (KERCADRS) 
ARYA Atherosclerosis  2015;11(1):14-20.
BACKGROUND
Along with the established effects of opium on metabolic parameters, stimulatory or inhibitory effects of opium on metabolic syndrome are also predictable. This study aimed to examine the association of opium use with metabolic syndrome and its components.
METHODS
This study was conducted on 5332 out of 5900 original sample participants enrolled in a population-based cohort entitled the Kerman Coronary Artery Disease Risk Study in Iran from 2009 to 2011. The subjects were divided into three groups of “non-opium users” (NOUs = 4340 subjects), “former opium users” (FOUs = 176 subjects), and dependent and occasional people named “current opium users” (COUs = 811 subjects). Metabolic syndrome was defined according to two International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) definition criteria.
RESULTS
The overall prevalence of IDF defined-metabolic syndrome among NOUs, FOUs, and COUs was 36.4%, 27.3%, and 39.0%, respectively; which was significantly higher in the COUs group (P = 0.012). However, no significant difference was revealed across the three groups in prevalence of NCEP defined-metabolic syndrome (NOUs = 37.2%, FOUs = 30.1%, and COUs = 39.6%, P = 0.058). The odds for IDF defined-metabolic syndrome was higher in both COUs [odd ratio (OR) = 1.28, P = 0.028)] and FOUs (OR = 1.57, P = 0.045) compared with NOUs as the reference adjusting gender, age, body mass index, and cigarette smoking. However, the appearance of NCEP defined-metabolic syndrome could not be predicted by opium use.
CONCLUSION
Opium use can be associated with an increased risk for metabolic syndrome based on IDF criteria and thus preventing the appearance of metabolic syndrome by avoiding opium use can be a certain approach to preventing cardiovascular disease.
PMCID: PMC4460348  PMID: 26089926
Metabolic Syndrome; Opium; Substance Abuse; Addictive Behavior
7.  Elevated Plasma Homocysteine Concentration in Opium-Addicted Individuals 
Addiction & Health  2015;7(3-4):149-156.
Background
Although the triggering role of both opium use and elevated plasma homocysteine level for progressing atherosclerosis and, therefore, appearing coronary heart disease has been clearly determined, no study are available with respect to the relation between these to risk profiles. In the present study and for the first time, we hypothesized that the opium addiction can be potentially correlated with elevated homocysteine concentration.
Methods
217 persons (103 opium-addicted and 114 non-addicted) were randomly selected from the Kerman Coronary Artery Disease Risk Study (KERCADRS), Iran, as a population-based, epidemiological prospective study. In all participants, an enzyme immunoassay kit was used to measure homocysteine in serum samples.
Findings
The serum level of homocysteine was significantly higher in the opium-addicted ones compared to non-addicted individuals (11.49 ± 7.45 vs. 8.02 ± 3.87 μmol/l) (P < 0.001). In this regard, 21.3% of the opium users and only 3.2% of the non-users had homocysteine concentration > 15 μmol/l (P < 0.001). On the other hand, individuals addicted to opiates exhibited significantly elevated odds of having homocysteine level higher than 15 [odds ratio (OR) = 8.244, 95% confidence interval (CI) = 3.117-21.806]. Multivariable linear regression model showed that the opium addiction could strongly predict elevated homocysteine level in the study individuals [beta = 3.524, standard error (SE) = 0.852] (P < 0.001).
Conclusion
Opium consumption can be strongly accompanied with the elevation of plasma homocysteine concentration, and thus opium addiction can exhibit elevated odds of having hyperhomocysteinemia.
PMCID: PMC4741235  PMID: 26885351
Opium addiction; Homocysteine; Cardiovascular disease
8.  Opium use during pregnancy and risk of preterm delivery: A population-based cohort study 
PLoS ONE  2017;12(4):e0176588.
Background
Use of narcotic or “recreational” drugs has been associated with adverse pregnancy outcomes such as preterm delivery. However, the associations might be confounded by other factors related to high-risk behaviours. This is the first study to investigate the association between traditional opium use during pregnancy and risk of preterm delivery.
Method and findings
We performed a population-based cohort study in the rural areas of the Golestan province, Iran between 2008 and 2010. We randomly selected 920 women who used (usually smoked) opium during pregnancy and 920 women who did not. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations between the opium use during pregnancy and preterm delivery and adjustment was made for potential confounding factors. This study shows compared with non-use of opium and tobacco, use of only opium during pregnancy was associated with an increased risk of preterm delivery (OR = 1.56; 95% CI 1.05–2.32), and the risk was more than two-fold increased among dual users of opium and tobacco (OR = 2.31; 95% CI 1.37–3.90). We observed that opium use only was associated with a doubled risk for preterm caesarean delivery (OR = 2.05; 95% CI 1.10–3.82) but not for preterm vaginal delivery (OR = 1.25; 95% CI 0.75–2.07). Dual use of opium and tobacco was associated with a substantially increased risk of vaginal preterm delivery (OR = 2.58; 95% CI 1.41–4.71).
Conclusions
Opium use during pregnancy among non-tobacco smokers is associated with an increased risk of preterm caesarean delivery, indicating an increased risk of a compromised foetus before or during labour. Women who use both opium and smoked during pregnancy have an increased risk of preterm vaginal delivery, indicating an increased risk of spontaneous preterm delivery.
doi:10.1371/journal.pone.0176588
PMCID: PMC5407680  PMID: 28448546
9.  Effects of Opium Addiction and Cigarette Smoking on Hematological Parameters 
Addiction & Health  2016;8(3):179-185.
Background
The aim of the present study was to investigate the effects of opium addiction and cigarette smoking on the complete blood count (CBC).
Methods
Eighty-six male subjects, including 31 opium-addicted cigarette smokers (OACS), 19 opium-addicted non-cigarette smokers (OANCS), 17 non-opium-addicted cigarette smokers (NOACS), and 19 non-opium-addicted non-cigarette smokers (NOANCS) participated in this study. The CBC test was measured in all individuals.
Findings
The OACS had significantly higher white blood cell (WBC), lymphocyte, and red blood cell (RBC) count but lower in mean corpuscular volume (MCV) compared to NOANCS. The OANCS had significantly higher lymphocyte in comparison with NOACS. Our results demonstrated that the number of WBC, lymphocytes, and RBC were significantly higher, while, MCV was lower in OANCS subjects when compared to NOACS. The OACS had significantly higher level of lymphocyte in comparison with NOACS. The mean number of lymphocyte in OANCS was found significantly higher than NOACS. The smokers were shown to have significantly higher levels of WBC compared to NOANCS.
Conclusion
Our results showed that opium-addiction, especially when associated with cigarette smoking, has intensive effects on hematological factors and these alteration might leads to greater risk for developing atherosclerosis, cardiovascular diseases, and imbalance in immune system.
PMCID: PMC5422014
Cigarette smoking; Addiction; Opium; Complete blood count
10.  Occupation, smoking, opium, and bladder cancer: A case–control study 
South Asian Journal of Cancer  2015;4(3):111-114.
Purpose:
The aim of this study was to investigate occupational risk factors associated with bladder cancer.
Materials and Methods:
In this case–control study, control group included patients who referred to a specialized clinic in the same city and hospitals where patients had been registered. Data were entered into SPSS software. Odds ratios (OR) were calculated for occupational variables and other characteristics. Then, using logistic regression, the association between cancer and drugs was studied while smoking was controlled.
Results:
Cigarette smoking, even after quitting, was also associated with bladder cancer (OR = 2.549). Considering the classification of occupations, the OR of working in metal industry in patients was 10.629. Multivariate analysis showed that use of the drug by itself can be a risk factor for bladder cancer. Drug abuse together with the control of smoking increased the risk of bladder cancer by 4.959.
Conclusion:
According to the findings of this study, contact with metal industries such as welding, and working with tin was found as a risk factor for bladder cancer. In addition, cigarette smoking and opium abuse individually were associated with bladder cancer.
doi:10.4103/2278-330X.173174
PMCID: PMC4756483  PMID: 26942139
Bladder cancer; cigarette; drugs; occupational factors; risk factors
11.  Opium dependency and in-hospital outcome of acute myocardial infarction 
Background: Impact of substance abuse on outcome of hospitalized patients with acute myocardial infarction (MI) is a frequent question. Available studies show disagreements over its impact, thus we performed this study to find a clear answer.
Methods: In a cross sectional study, 304 patients (include 152 consecutive opium dependents and equal number of independents) with acute MI admitted to coronary care units (CCU) in Bou-Ali Sina Hospital of Qazvin University of Medical Science were enrolled. Data on demographics (e.g. age, sex and education), identified MI risk factor (smoking and diabetes), clinical findings (e.g. Killip class and in-hospital mortality), ECG findings (e.g. localization of infarction and arrhythmia), echocardiographic examinations (e.g. ejection fraction and regional wall motion abnormality) and laboratory findings (lipid profile, glycemic situation) were gathered.
Results: The mean age was 63.01±12 years for opium users and 64.3± 10 for non-users. Educational level was higher in patients who used opium. No significant differences were found between opium users and non-users in rate of hypertension, diabetes mellitus, hyperlipidemia, and cigarette smoking. The mean duration of experienced chest pain in hospital stay was significantly higher in non-opium users compared to opium users (1.78± 0.63 vs.1.52±0.54) (p< 0.001). Higher Killip class and arrhythmia have been identified as the most important independent predictors of early in-hospital mortality (in both groups).
Conclusion: The higher Killip class and age identified as the most important independent predictors of early in-hospital mortality and addiction do not act as a major risk or protecting factor in this context. Nevertheless, we believe that a more comprehensive study with follow up of patients should be carried out for evaluation of opium addicted patients, their outcome after MI, and a better decision making for their treatment.
PMCID: PMC4313445  PMID: 25679001
Opium dependence; Myocardial infarction; Outcome
12.  Can Opium Use Contribute to a Higher Risk of Colorectal Cancers? A Matched Case-control Study in Iran 
Iranian Journal of Public Health  2016;45(10):1322-1331.
Background:
Colorectal cancers (CRCs) including colon, rectum and anal cancers are the third most prevalent cancers in the world. There are strong evidence showing the risk of the cigarette smoking, alcohol use, low physical activity and some types of diets in CRCs; however, few studies explored the relationship between opium use and CRCs. This study aimed to investigate the association between opioid use and the incidence of CRCs.
Methods:
In a population-based matched case-control study in Kerman, Iran, 175 patients with colorectal cancers and 350 healthy controls (matched for age, sex, and place of residence) were interviewed from Sep 2014 to Nov 2014. Opium and its derivatives, cigarette, alcohol, and diet use were collected using a valid and reliable questionnaire. Conditional logistic regression was used to estimate odds ratios with 95% confidence intervals.
Results:
The use of opioids was associated with an increased risk of CRCs (adjusted odds ratio= 4. 5, 95% CI: 2. 4–8. 7). In addition, a dose-response relationship was observed between the cumulative use of opioids and the incidence of CRCs (with low use OR=3. 7; 95% CI: 1. 5–8. 6 and high use OR= 8. 0; 95% CI: 2. 9–21. 7). This dose-response relationship was also strong in patients with colon cancers, with OR= 3. 9 (95% CI: 1. 5–9. 9) and 9. 4 (95% CI: 3. 3–27. 0) for the low and high uses of opioids, respectively.
Conclusion:
Opioid use can lead to an increased risk of CRCs. Therefore, it is necessary to implement preventive policies to control the use of opioids.
PMCID: PMC5149496  PMID: 27957439
Risk factor; Colorectal cancers; Opioid; Case-control; Iran
13.  The effect of opium addiction on thyroid function tests 
Background
A number of abnormalities has been identified among drug addicted users especially heroin addicts. However, there are a few studies to assess the opium effects on thyroid hormones. the aim of the present study is to investigate the effect of opium on the thyroid function tests.
Method
In this case–control, 50 male addicts, aged 20–50 years, with history of addiction to opium lasting more than two years, and 50 male non-addicts as control group were randomly selected. 10 cc blood sample was taken for measurements of TSH, total T4 and T3, free T4 and T3, and T3 resin uptake (T3RU) and 50 cc urine sample for opium testing.
Results
The univariate analysis revealed that there was not a significant association between opium and serum levels of T4 and TSH, but compared with control group, a slight increase in total T3 and a decrease in T3RU were observed among addicts (P < 0.05). In multivariate analysis, opium was also found to exert a lowering effect on serum free T4 level after adjusting of age and cigarette smoking (P < 0.05).
Conclusion
The findings of the present study demonstrated that opium can influence on thyroid function by increasing total T3 and decreasing T3RU and free T4 levels.
doi:10.1186/2251-6581-13-5
PMCID: PMC3922854  PMID: 24393239
Opium; Thyroid function test; Free T4
14.  Stroke Modifies Drug Consumption in Opium Addicts: Role of the Insula 
Basic and Clinical Neuroscience  2013;4(4):307-314.
Introduction
Addiction imposes a large medical, social and economic burden on societies. Currently, there is no effective treatment for addiction. Our struggle to decipher the different mechanisms involved in addiction requires a proper understanding of the brain regions which promote this devastating behavior. Previous studies have shown a pivotal role for insula in cigarette smoking. In this study we investigated the change in opium consumption after CVA.
Methods
This study took place in three referral academic hospitals affiliated to Tehran University of Medical Sciences. Patients who suffered a CVA and were addicted to opium were recruited during their hospitalization or visit to the neurology clinic in this study. Age, sex and the route and mean amount of opium use of each patient before CVA and 1, 3 and 6 months post-CVA was asked using a questionnaire. The patients were divided into three groups based on the location of brain ischemia (insula, basal ganglia and non-insula non-basal ganglia group).
Results
Seventy five percent of the patients with ischemia of the insula changed the route or amount of opium use after CVA and 37.5% of them stopped opium use after CVA. These values were significantly higher than patients with non-insula nonbasal ganglia ischemia (p values 0.005 and 0.03 for change in route or amount and stopping opium use, respectively). This was not true in patients with ischemia of the basal ganglia. Younger patients were more likely to change the route or amount of opium use and stop opium use after CVA (p values 0.002 and 0.026, respectively).
Discussion
The results of the present study indicate a possible role for the insula in opium addiction, especially in younger individuals.
PMCID: PMC4202575  PMID: 25337362
Stroke; Addiction; Opium
15.  A Case-Control Study of Comparison of Plasma Levels of Matrix Metalloproteinase-9 in Inhaled Opium Addicts and Clinically Healthy Persons 
Addiction & Health  2017;9(1):11-16.
Background
Metalloproteinase-9 exists in the basement membrane of normal tissues and is a major factor in cancer invasion and lymphatic metastasis. Smoking has been reported to increase the metalloproteinase level, but the role of opium consumption in metalloproteinase level has not yet been examined. The current research intended to examine the impacts of opium consumption on the serum levels of metalloproteinase.
Methods
This case-control research was conducted in Kerman (in the southeast of Iran), after getting medical approve by the ethics committee. Case group of 33 non-smokers with no active inflammatory diseases who had the experience of inhaled opium and its derivatives were compared with a control group of 40 non-smokers with no active inflammatory disease and no experience of inhaled opium and its derivatives. Student’s t-test, mean, and chi-square test were employed to determine the correlation between the variables.
Findings
No statistically meaningful variation was detected in plasma metalloproteinase concentration between the case and control groups (P = 0.160). Also, there was no significant relation between the plasma metalloproteinase concentration and urinary morphine in case groups (P = 0.410), but a statistically significant correlation was found between gender and metalloproteinase in both the case and control groups (P = 0.003).
Conclusion
According to the possible role of opioid drugs in cancer and its prognosis both directly and through their impact on serum levels of metalloproteinase, further studies are suggested.
PMCID: PMC5628763
Metalloproteinase; Opium; Case-control studies; Iran
16.  Blood Lead Levels in Asymptomatic Opium Addict Patients; a Case Control Study 
Emergency  2017;5(1):e69.
Introduction:
One of the newest non-occupational sources of lead contamination is drug addiction, which has recently been addressed as a major source of lead poisoning in some countries. The present study aimed to investigate the blood lead level (BLL) of asymptomatic opium addicts.
Methods:
This case-control study was conducted during a one-year period to compare BLL of three groups consisting of opium addicts, patients under methadone maintenance therapy (MMT), and healthy individuals.
Results:
99 participants with the mean age of 55.43±12.83 years were studied in three groups of 33 cases (53.5% male). The mean lead level in opium addicts, MMT and control groups were 80.30 ± 6.03 μg/L, 67.94 ± 4.42 μg/L, and 57.30±4.77 μg/L, respectively (p=0.008). There was no significant difference in BLL between MMT and healthy individuals (p=0.433) and also between opium addicts and MMT individuals (p=0.271).Oral opium abusers had significantly higher lead levels (p = 0.036). There was a significant correlation between BLL and duration of drug abuse in opium addict cases (r=0.398, p=0.022). The odds ratio of having BLL ≥ 100 in oral opium users was 2.1 (95% CI: 0.92 - 4.61; p = 0.43).
Conclusion:
Based on the result of present study, when compared to healthy individuals, opium addicts, especially those who took substance orally had significantly higher levels of blood lead, and their odds of having BLL ≥ 100 was two times. Therefore, screening for BLL in opium addicts, particularly those with non-specific complaints, could be useful.
PMCID: PMC5585839
Lead; substance abuse treatment centers; methadone; opium; heroin; case-control studies
17.  Outcomes and long-term survival of coronary artery surgery: The controversial role of opium as risk marker 
World Journal of Cardiology  2016;8(11):676-683.
AIM
To study survival in isolated coronary artery bypass graft (CABG) patients and to evaluate the impact of preoperative chronic opium consumption on long-term outcome.
METHODS
Cohort of 566 isolated CABG patients as Tehran Heart Center cardiac output measurement was conducted. Daily evaluation until discharge as well as 4- and 12-mo and 6.5-year follow-up information for survival status were fulfilled for all patients. Long-term 6.5-year overall and opium-stratified survival, adjusted survival curves based on opium consumption as well as possible predictors of all-cause mortality using multiple cox regression were determined by statistical analysis.
RESULTS
Six point five-year overall survival was 91.8%; 86.6% in opium consumers and 92.7% in non-opium consumers (P = 0.035). Patients with positive history of opium consumption significantly tended to have lower ejection fraction (EF), higher creatinine level and higher prevalence of myocardial infarction. Multiple predictors of all-cause mortality included age, body mass index, EF, diabetes mellitus and cerebrovascular accident. The hazard ratio (HR) of 2.09 for the risk of mortality in opium addicted patients with a borderline P value (P = 0.052) was calculated in this model. Further adjustment with stratification based on smoking and opium addiction reduced the HR to 1.20 (P = 0.355).
CONCLUSION
Simultaneous impact of smoking as a confounding variable in most of the patients prevents from definitive judgment on the role of opium as an independent contributing factor in worse long-term survival of CABG patients in addition to advanced age, low EF, diabetes mellitus and cerebrovascular accident. Meanwhile, our findings do not confirm any cardio protective role for opium to improve outcome in coronary patients with the history of smoking. Further studies are needed to clarify pure effect of opium and warrant the aforementioned findings.
doi:10.4330/wjc.v8.i11.676
PMCID: PMC5124726  PMID: 27957254
Coronary artery bypass; Outcomes; Survival analysis; Opium; Hazards models
18.  Opium, tobacco, and alcohol use in relation to oesophageal squamous cell carcinoma in a high-risk area of Iran 
British Journal of Cancer  2008;98(11):1857-1863.
The very high incidence of oesophageal squamous cell carcinoma (ESCC) in Golestan Province in northeastern Iran was suggested by studies in the 1970s as partly due to opium use, which is not uncommon in this area, but based on limited numbers. From December 2003 to June 2007, we administered a validated structured questionnaire to 300 ESCC cases and 571 controls, matched on neighbourhood of residence, age (±2 years), and sex. We used conditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusted for potential confounders. Compared with those who used neither tobacco nor opium, risk of ESCC was increased in those who used tobacco only (OR, 95% CI: 1.70, 1.05–2.73), in those who used opium only (2.12, 1.21–3.74), and in those who used both tobacco and opium (2.35, 1.50–3.67). All forms of tobacco use (cigarettes, hookah, and nass) were associated with higher ESCC risk. Similarly, use of both crude opium and other forms of opium were associated with higher risk. Alcohol consumption was seen in only 2% of the cases and 2% of the controls, and was not associated with ESCC risk.
doi:10.1038/sj.bjc.6604369
PMCID: PMC2410115  PMID: 18475303
oesophageal cancer; Iran; opium; tobacco; alcohol
19.  Opium use and mortality in Golestan Cohort Study: prospective cohort study of 50 000 adults in Iran 
Objectives To investigate the association between opium use and subsequent risk of death.
Design Prospective cohort study.
Setting The Golestan Cohort Study in north-eastern Iran collected detailed validated data on opium use and other exposures at baseline. Participants were enrolled between January 2004 and June 2008 and were followed to May 2011, with a follow-up success rate of over 99%.
Participants 50 045 participants aged 40-75 at baseline.
Main outcomes Mortality, all cause and major subcategories.
Results 17% (n=8487) of the participants reported opium use, with a mean duration of 12.7 years. During the follow-up period 2145 deaths were reported. The adjusted hazard ratio for all cause mortality associated with ever use of opium was 1.86 (95% confidence interval 1.68 to 2.06). Opium consumption was significantly associated with increased risks of deaths from several causes including circulatory diseases (hazard ratio 1.81) and cancer (1.61). The strongest associations were seen with deaths from asthma, tuberculosis, and chronic obstructive pulmonary disease (11.0, 6.22, and 5.44, respectively). After exclusion of people who self prescribed opium after the onset of major chronic illnesses, the associations remained strong with a dose-response relation.
Conclusion Opium users have an increased risk of death from multiple causes compared with non-users. Increased risks were also seen in people who used low amounts of opium for a long period and those who had no major illness before use.
doi:10.1136/bmj.e2502
PMCID: PMC3328545  PMID: 22511302
20.  Opium use and mortality in Golestan Cohort Study: prospective cohort study of 50 000 adults in Iran 
The BMJ  2012;344:e2502.
Objectives To investigate the association between opium use and subsequent risk of death.
Design Prospective cohort study.
Setting The Golestan Cohort Study in north-eastern Iran collected detailed validated data on opium use and other exposures at baseline. Participants were enrolled between January 2004 and June 2008 and were followed to May 2011, with a follow-up success rate of over 99%.
Participants 50 045 participants aged 40-75 at baseline.
Main outcomes Mortality, all cause and major subcategories.
Results 17% (n=8487) of the participants reported opium use, with a mean duration of 12.7 years. During the follow-up period 2145 deaths were reported. The adjusted hazard ratio for all cause mortality associated with ever use of opium was 1.86 (95% confidence interval 1.68 to 2.06). Opium consumption was significantly associated with increased risks of deaths from several causes including circulatory diseases (hazard ratio 1.81) and cancer (1.61). The strongest associations were seen with deaths from asthma, tuberculosis, and chronic obstructive pulmonary disease (11.0, 6.22, and 5.44, respectively). After exclusion of people who self prescribed opium after the onset of major chronic illnesses, the associations remained strong with a dose-response relation.
Conclusion Opium users have an increased risk of death from multiple causes compared with non-users. Increased risks were also seen in people who used low amounts of opium for a long period and those who had no major illness before use.
doi:10.1136/bmj.e2502
PMCID: PMC3328545  PMID: 22511302
21.  Effects of opium consumption on coronary artery disease risk factors and oral health: Results of Kerman Coronary Artery Disease Risk factors Study a population-based survey on 5900 subjects aged 15-75 years 
Background:
Opium abuse as a relatively common behavior among Iranian population may have an association with the other coronary artery disease (CAD) risk factors. Here, we reported the prevalence of opium abuse and its co-exposures with oral health and other CAD risk factors.
Methods:
We recruited 5900 inhabitant aged 15-75 years using a randomized cluster household survey. All were interviewed for level of physical activity (PA), depression, anxiety and opium use and assessed for hypertension, diabetes, hyperlipidemia, and oral health status. Regarding to opium abuse, participants were grouped into: “Non-,” “occasional,” and “dependent” users. Using logistic regression model for every CAD risk factor, we assessed whether the co-exposure of opium and CAD risk factor is significant.
Results:
Overall, 10.6% reported ever opium use including 5.6% dependent and 5% occasional users. The prevalence of opium abuse was increased from 2.1% in 15-25 years to 24.5% in 55-64 years group. Opium abuse, in occasional and dependent forms, was associated with depression (adjusted odds ratio [AOR] 1.81 and 2.49) and low PS (AOR 1.43 and 1.71 respectively). Dependents were less obese than nonusers (P < 0.01). Opium abuse had no significant association with hypertension, diabetes, oral health status and lipid profile.
Conclusions:
Opium abuse was associated with depression and low PA. No ameliorative effect was observed on hypertension, diabetes, and plasma lipid profile. Therefore, positive association of opium with depression and LPA and the incorrectness of belief on its ameliorative effect on three other important risk factors of CAD should be clearly highlighted in public health messages to the community.
doi:10.4103/2008-7802.157470
PMCID: PMC4455126  PMID: 26097671
Coronary artery disease; opium addiction; prevalence; risk factors
22.  Does Opium Dependency Affect the Pattern of Involvement in Laryngeal Cancer? 
Introduction:
Laryngeal cancer is the second most common cancer involving the respiratory tract, second only to lung cancer. Previous studies have shown opium dependency to be a possible risk factor for laryngeal cancer. Opium consumption is a major problem in some parts of the world. The aim of this study was to investigate the effect of opium consumption on the pattern of involvement in laryngeal cancer.
Methods and materials:
In this analytical cross-sectional study, 44 patients diagnosed with laryngeal cancer (41 male and three female) were studied. Data were collected using a questionnaire, physical examination, and paraclinical studies. Patients were defined as opium dependent based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) criteria and duration of opium consumption.
Results:
Patients were categorized into two groups: opium-dependent (32.6%) and non-opium-dependent (67.4%) patients. The average age of the patients was 58.5±3.2 years in the opium-dependent group and 60.7±2.8 years in the non-opium-dependent group (P=non-significant). An analysis of the pattern of involvement in each group showed glottis involvement in 56%, subglottis involvement in 8%, supraglottis involvement in 32%, and hypopharyngeal involvement in 4% of the opium-dependent group compared with glottis involvement in 55.9%, subglottis involvement in 11.8%, supraglottis involvement in 32.4%, and hypopharyngeal involvement in none of the non-opium-dependent group (P=non-significant).
Conclusion:
There was a poor correlation between opium dependency and pattern of involvement in laryngeal cancer. Opium dependency did not lead to the development of laryngeal cancer at a younger age, based on our study.
PMCID: PMC5168575  PMID: 28008394
Iran; Laryngeal cancer; Opium
23.  Determinants of Gastroesophageal Reflux Disease, Including Hookah Smoking and Opium Use– A Cross-Sectional Analysis of 50,000 Individuals 
PLoS ONE  2014;9(2):e89256.
Background
Gastroesophageal reflux disease (GERD) is a common cause of discomfort and morbidity worldwide. However, information on determinants of GERD from large-scale studies in low- to medium-income countries is limited. We investigated the factors associated with different measures of GERD symptoms, including frequency, patient-perceived severity, and onset time.
Methods
We performed a cross-sectional analysis of the baseline data from a population-based cohort study of ∼50,000 individuals in in Golestan Province, Iran. GERD symptoms in this study included regurgitation and/or heartburn.
Results
Approximately 20% of participants reported at least weekly symptoms. Daily symptoms were less commonly reported by men, those of Turkmen ethnicity, and nass chewers. On the other hand, age, body mass index, alcohol drinking, cigarette smoking, opium use, lower socioeconomic status, and lower physical activity were associated with daily symptoms. Most of these factors showed similar associations with severe symptoms. Women with higher BMI and waist to hip ratio were more likely to report frequent and severe GERD symptoms. Hookah smoking (OR 1.34, 95% CI 1.02–1.75) and opium use (OR 1.70, 95% CI 1.55–1.87) were associated with severe symptoms, whereas nass chewing had an inverse association (OR 0.87, 95% CI 0.76–0.99). After exclusion of cigarette smokers, hookah smoking was still positively associated and nass chewing was inversely associated with GERD symptoms (all frequencies combined).
Conclusion
GERD is common in this population. The associations of hookah and opium use and inverse association of nass use with GERD symptoms are reported for the first time. Further studies are required to investigate the nature of these associations. Other determinants of GERD were mostly comparable to those reported elsewhere.
doi:10.1371/journal.pone.0089256
PMCID: PMC3931722  PMID: 24586635
24.  Is Opium a Real Risk Factor for Esophageal Cancer or Just a Methodological Artifact? Hospital and Neighborhood Controls in Case-Control Studies 
PLoS ONE  2012;7(3):e32711.
Background
Control selection is a major challenge in epidemiologic case-control studies. The aim of our study was to evaluate using hospital versus neighborhood control groups in studying risk factors of esophageal squamous cell carcinoma (ESCC).
Methodology/Principal Findings
We compared the results of two different case-control studies of ESCC conducted in the same region by a single research group. Case definition and enrollment were the same in the two studies, but control selection differed. In the first study, we selected two age- and sex-matched controls from inpatient subjects in hospitals, while for the second we selected two age- and sex-matched controls from each subject's neighborhood of residence. We used the test of heterogeneity to compare the results of the two studies. We found no significant differences in exposure data for tobacco-related variables such as cigarette smoking, chewing Nass (a tobacco product) and hookah (water pipe) usage, but the frequency of opium usage was significantly different between hospital and neighborhood controls. Consequently, the inference drawn for the association between ESCC and tobacco use did not differ between the studies, but it did for opium use. In the study using neighborhood controls, opium use was associated with a significantly increased risk of ESCC (adjusted OR 1.77, 95% CI 1.17–2.68), while in the study using hospital controls, this was not the case (OR 1.09, 95% CI 0.63–1.87). Comparing the prevalence of opium consumption in the two control groups and a cohort enrolled from the same geographic area suggested that the neighborhood controls were more representative of the study base population for this exposure.
Conclusions/Significance
Hospital and neighborhood controls did not lead us to the same conclusion for a major hypothesized risk factor for ESCC in this population. Our results show that control group selection is critical in drawing appropriate conclusions in observational studies.
doi:10.1371/journal.pone.0032711
PMCID: PMC3291619  PMID: 22396792
25.  The effect of opium addiction on serum adiponectin and leptin levels in male subjects: a case control study from Kerman Coronary Artery Disease Risk Factors Study (KERCADRS) 
EXCLI Journal  2013;12:916-923.
Objectives: Serum adiponectin and leptin levels have been shown to be related to obesity, insulin resistance and cardiovascular diseases (CVD). Opium addiction has a positive association with endocrine system disorders. The relationship between adipokines and opium addiction is unclear. In the present study, we aimed to determine serum adiponectin and leptin levels in opium addicted subjects.
Methods: 176 men, 88 opium addicts and 88 non- addicts were randomly selected from subjects who participated in Kerman Coronary Artery Disease Risk factors Study (KERCADRS); a population-based study. Serum adiponectin and leptin levels were measured using ELISA and compared between two groups. We adjusted the effect of some confounding factors such as the patients' demographic, clinical and medical history in multivariate analysis model.
Results: The serum level of adiponectin in opium addicts was significantly lower than control group (6.5±3.6 vs. 9.8±8.1 µg/ml, P<0.001). There was no significant difference in serum leptin level between two groups (11.8±10.3 ng/ml in control group vs. 11.5±10.8 ng/ml in opium addicts, p = 0.80). In the multivariate analysis, after adjusting for age, cigarette smoking, body mass index, type 2 diabetes, hypertension, cholesterol, triglyceride and high and low density lipoproteins, the negative association between opium addiction and decreased adiponectin level was still present (β = -0.144, P value = 0.005).
Conclusions: The results showed that opium addiction reduces serum adiponectin level. Since adiponectin has been shown to have anti-diabetic and anti-atherogenic effects, its reduction may account for increase in the risk of metabolic disorders such as insulin resistance and CVD amongst opium addicted patients.
PMCID: PMC4822307  PMID: 27065765
opium addiction; leptin; adiponectin; cardiovascular diseases

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