Opium and Cigarette Smoking are Independently Associated with Bladder Cancer: The Findings of a Matched Case - Control Study.

BACKGROUND: Bladder cancer disproportionally affects the communities. While it is the ninth most common cancer in the world, in some parts of Iran including Kerman province it is the most common cancer among men. This study aimed to determine potential risk factors of bladder cancer in Kerman province, Iran. METHODS: During February to July 2020, in this matched hospital-based case-control study, 100 patients with bladder cancer and 200 healthy individuals (matched in age and sex) were recruited. Socio-demographics status, occupational exposures, common diet, history of drug use and family history of cancer, were collected using a structured questionnaire. Bivariable and multivariable logistic regression were applied and crude and adjusted odds ratios (AOR) along with their 95% confidence intervals (95%CI) were calculated. Data were analyzed using Stata version 14 software. RESULTS: Opium consumption, cigarette smoking and low level of income were associated with increased chance of bladder cancer. Compared to never use, use of opium up to 18000 Gram -year was associated with increased chance of bladder cancer (AOR: 6; 95% CI =2.3, 15.5). The chance was higher among those who used opium more than 18,000 Gram - year (AOR: 11.3; 95% CI =2.3, 15.5). In comparison with never smokers, the chance of bladder cancer increased among those who smoked up to 20 pack-year cigarette) (AOR: 3.4; 95%CI= 1.3, 8.9) and those who smoke ≥ 20 pack-year (AOR: 15.8; 95% CI= 5.9, 42.4). CONCLUSIONS: The observed strong dose-response association between opium consumption, cigarette smoking and bladder cancer highlights the need for extension of harm reduction programs especially in regions with high burden of disease.

Effects of methadone, opium tincture and buprenorphine maintenance therapies on thyroid function in patients with OUD.

Various types of medications are used as maintenance therapies for substance use disorder; However, the side effects of these drugs are shown to restrict their use and increase the risk of relapse in patients. As a result, alternative maintenance therapies are tested in the hope for optimum therapy. Since opium tincture is a new and innovative maintenance treatment in Iran, we attempted to compare the therapeutic and side effects of opium tincture with two standard therapies, i.e., methadone and buprenorphine. Hence, thyroid function was tested in three methods of maintenance therapies with methadone, buprenorphine, and opium tincture in a cross-sectional study. In this study, 150 patients with the mean age of 51.63 ± 13.56 years and a history of opioid or opioid-derivatives use disorder, underwent the maintenance treatment with methadone, buprenorphine, and opium tincture at Bojnurd Addiction Treatment Centers in northeastern Iran. These patients were selected using convenience sampling. Then, they were placed into three treatment groups of methadone, buprenorphine, and opium tincture. The thyroid functionality was assessed with measuring TSH, fT4, fT3, T3RU, and Anti TPO, carried out in a reference laboratory. Finally, these data were analyzed by ANOVA using SPSS.16 software. The results showed that there was no significant difference in the average levels of TSH, fT3, fT4, and Anti TPO in these treatment groups; except for T3RU concentration, which was increased significantly in the opium tincture group as compared to the methadone treated group. Also, the frequency of fT4, and T3RU disorders demonstrated a significant change in three groups. The findings of the present study demonstrated that opium tincture in comparison with methadone could increase T3RU levels resulting in euthyroidism possibly through TBG.

An Exploratory Study of Units of Reporting Opium Usein Iran: Implications for Epidemiologic Studies.

BACKGROUND: Measuring the amount of opium use is a challenge in epidemiologic studies. Self-report of amount of opium use at each consumption, widely used in the literature, usually fails to provide a good estimate. The purpose of this study is to systematically study the perceived weight units of reported opium use in Iran, and compare them to the standardized units of weight measurement. METHODS: An exploratory descriptive study was conducted in six major cities of Iran. Study participants were interviewed and asked to use a Play-Doh-like material to demonstrate the amount of opium they use. To obtain an estimate of the weight of the material used, we multiplied the volume by the density of the opium product. We experimentally determined the density of the commonly used opium products. We used medians and inter-quartile ranges (IQRs) to report the typical amount of each unit. RESULTS: A total of 108 individuals participated in this study. The most frequently reported unit was "gram"; the median perceived weight for one gram (g) of opium was 0.24 (IQR: 0.16) g. The second most commonly used unit was nokhod with a median of 0.16 (IQR: 0.16) g, followed by mesghaal and hab/habeh, which were 1.28 (IQR: 0.81) and 0.16 (IQR: 0.16) g, respectively. The median perceived weight of mesghaal and gram in the studied cities was less than the expected standardized values. CONCLUSION: In conclusion, the reported amount of opium use is highly inaccurate and unreliable, and is mainly subject to underestimation.

Lead poisoning due to ingestion of lead-contaminated opium: A diagnostic study on patients' imaging findings.

OBJECTIVES: Our study attempts to determine if for patients following ingestion of lead-contaminated opium, radiographs [plain X-ray (KUB)] or unenhanced computed tomography (CT scan) of the abdomen may be predictive of lead poisoning. METHODS: Our study is concerned with patients of >21 years with elevated lead concentrations, who had undergone KUB or CT. Patients with other toxicities who had undergone similar imaging profiles but who had low blood lead level (BLL) were enrolled as controls. RESULTS: We evaluated a total of 79 cases and 79 controls with median [IQR] BLLs of 126 [97.4, 160] µg/dL and 8.7 [5.5, 15] µg/dL. All cases and eleven controls (13.9%) were addicted to oral opium, and of these cases, anemia (94.9%) and abdominal pain (92.4%) were the two most common clinical manifestations. Two radiologists reviewed the X-ray and non-contrast CTs. Fifty (63.3%) and 53 (67.1%) cases and controls underwent CT scanning with 34 (68%) vs. 6 (11.3%) positive CTs (P < 0.001) while 43 (54.4%) and 39 (43.3%) underwent X-rays with 21 (48.8%) vs. 4 (11.8%) positive X-rays, respectively (P < 0.001). Positive CT is associated with BLL between 10 and 45 µg/dL with a specificity of 96.9%, 88.7% and positive predictive value of 97.5% and 85% respectively. CONCLUSIONS: In suspected cases of lead exposure due to ingested opium, and if BLL is not readily available, a positive imaging result may guide radiologists and physicians to consider lead poisoning.

Opioid Crisis Along Mexico's Northern Border: Treatment Needs Mexican Opioid Crisis.

BACKGROUND: Heroin production for external markets and low rates of use in Mexico have had a long history. A recent shift toward an increase in use and related problems calls for the evaluation of treatment needs in order to draw recommendations for policies. METHODS: The objectives were to identify predictors of choice of treatment and barriers to care among persons that had been with no treatment. The study included a convenience sample of 600 face-to-face interviews of people 18 years of age and older and a rapid HIV and HCV tests in three cities on Mexico's Northern Border: Ciudad Juárez, San Luis Río Colorado and Tijuana. The choice of treatment (methadone, other pubic or private treatments with no experience with methadone maintenance and only self-help or religious care), was analyzed though a multiple logistic multimodal regression analysis. Informed consents to be interviewed and for HIC and HIV were signed by interviewers. RESULTS: The majority of persons interviewed were males (89.7%) with an average age of 40. Having emigrated to the United States and a greater length of heroin use predicted seeking methadone treatment versus public or private treatment or informal care. The most important barriers to care were lack of information and stigma. HIC, HIV and other infectious and chronic diseases including depression were often unattended. CONCLUSIONS: There is a need to reform treatment policies in order to cover this w emerging and demanding problem.

Effectiveness of a Pre-emptive Preoperative Belladonna and Opium Suppository on Postoperative Urgency and Pain After Ureteroscopy.

PURPOSE: Postoperative ureteroscopy patients can develop bladder spasms, complaints of pain, and the urgent need to void during emergence from anesthesia. Discomfort leads to patient agitation, resulting in a risk to patient safety. The purpose of this study was to determine the effectiveness of a preemptive preoperative belladonna and opium (B + O) suppository on postoperative bladder comfort, narcotic requirements, and length of stay of ureteroscopy patients. DESIGN: A prospective double-blind study was conducted. METHODS: Fifty adult outpatients scheduled for ureteroscopy were assigned to routine care or a B + O suppository immediately after anesthesia induction. Urinary urgency and pain were assessed every 15 minutes. FINDINGS: Urgency significantly decreased in the B+O group, with less than half reporting urgency at discharge. CONCLUSIONS: Pre-emptive preoperative administration of a B + O suppository before ureteroscopy results in decreased urinary urgency during the postoperative recovery. Pre-emptive preoperative interventions can result in positive outcomes before discharge.

Oxidative stress in opium users after using lead-adulterated opium: The role of genetic polymorphism.

Use of lead-adulterated opium has become one of the major sources of lead poisoning in Iran. This study was designed to assess clinical effects and oxidative stress and its association with GSTM1, GSTT1, NQO1, and ALAD genes polymorphisms and blood lead level (BLL) in lead-adulterated opium users. The oxidative stress status in 192 opium users with lead poisoning symptoms measured and compared with 102 healthy individuals. Gluthatione S-transferase (GST)-M1 and -T1 genes deletion, NQO1 rs1800566, and δ-aminolevulinic acid dehydratase (ALAD) rs1800435 polymorphisms were determined using PCR and PCR-RFLP. The relation between the polymorphisms, BLL, and oxidative stress parameters were analysed using multivariate linear regressions. The common symptoms of lead toxicity were gastrointestinal and neurologic complications. Oxidative stress was significantly higher in opium addicts and lipid peroxidation significantly correlated with BLL. There was significant association between ALAD rs1800435 and BLL, and the BLL was significantly lower in the patients with ALAD 1-2 genotype. Use of lead-adulterated opium causes high frequency of lead toxicity symptoms, hematological and biochemical abnormalities, and oxidative stress which are associated with BLL. Route of opioid use and the polymorphism of rs1800435 in ALAD gene are the major determinants of BLL in lead-adulterated opium users.

Lead poisoning outbreak among opium users in the Islamic Republic of Iran, 2016-2017.

OBJECTIVE: To describe an outbreak of lead poisoning among opium users in the Islamic Republic of Iran and estimate the number of affected people in the country. METHODS: We used data from the country's largest poison treatment centre to illustrate the epidemiology of an outbreak of lead poisoning in oral opium users. We describe the government's referral and treatment guidelines in response to the outbreak. Based on the number of individuals treated and previous studies on the prevalence of oral opium use we estimated the total number of people at risk of lead-contaminated opium nationwide. FINDINGS: In February 2016, we noticed a steep increase in the numbers of oral opium users referred to our poison treatment centre with abdominal pain, anaemia and constipation. Numbers peaked in June 2016 but the outbreak was ongoing in August 2017. The mean blood lead level in a sample of 80 patients was 140.3 µg/dL (standard deviation: 122.6). Analysis of an illegal opium sample showed 3.55 mg lead in 1 g opium. Treatment was exposure reduction with opioid substitutes and laxatives, or chelation therapy if indicated. Over 7 months, 4294 poison cases were seen at main referral hospitals in Tehran out of an estimated 31 914 oral opium users in the city. We estimate more than 260 000 out of 773 800 users nationwide remain untreated and at risk of poisoning. CONCLUSION: Lead-contaminated opium and heroin that has transited through the Iranian markets is a global risk and highlights a need for better monitoring of illegal drug supplies.

Lead Toxicity due to Ingestion of Lead-Contaminated Opium in a Patient Presenting with Motor Neuropathy and Upper Limb Paresis: A case report.

Opium users may present with central or peripheral nervous system-related symptoms, gastrointestinal complications and anaemia; in such cases, lead poisoning should be suspected and chelation therapy initiated as soon as possible. We report a 64-year-old male patient with a 20-year history of opium addiction who was referred to the Imam Reza Hospital, Birjand, Iran, in 2017 with severe motor neuropathy and paresis in both upper limbs. His primary symptoms were generalised weakness, abdominal and bone pain, constipation and lower limb paraesthesia that had started several months prior. In addition, he reported severe progressive bilateral paresis of the upper limbs of one month's duration. A diagnosis of lead poisoning was confirmed by a blood lead level of 140 µg/dL. The patient underwent chelation therapy after which he improved significantly. At a one-year follow-up visit, he was neurologically intact and symptom-free.

An interesting case of opium tea toxicity.

We present an unusual cause of respiratory arrest resulting from sole ingestion of home-brewed opium tea. A 64-year-old woman was found unresponsive and in respiratory arrest by a first responder. There were no obvious signs of regular recreational drug use. On presentation to the local district general hospital, the patient was in extremis, with severe physiological and biochemical derangements. A naloxone infusion was commenced and she later made a good recovery. It was subsequently discovered that she had brewed opium tea from opium buds she had picked from a nearby commercial poppy farm, a practice she had learnt while in Afghanistan.

Randomized controlled trial of postoperative belladonna and opium rectal suppositories in vaginal surgery.

BACKGROUND: After vaginal surgery, oral and parenteral narcotics are used commonly for pain relief, and their use may exacerbate the incidence of sedation, nausea, and vomiting, which ultimately delays convalescence. Previous studies have demonstrated that rectal analgesia after surgery results in lower pain scores and less intravenous morphine consumption. Belladonna and opium rectal suppositories may be used to relieve pain and minimize side effects; however, their efficacy has not been confirmed. OBJECTIVE: We aimed to evaluate the use of belladonna and opium suppositories for pain reduction in vaginal surgery. MATERIALS AND METHODS: A prospective, randomized, double-blind, placebo-controlled trial that used belladonna and opium suppositories after inpatient or outpatient vaginal surgery was conducted. Vaginal surgery was defined as (1) vaginal hysterectomy with uterosacral ligament suspension or (2) posthysterectomy prolapse repair that included uterosacral ligament suspension and/or colporrhaphy. Belladonna and opium 16A (16.2/60 mg) or placebo suppositories were administered rectally immediately after surgery and every 8 hours for a total of 3 doses. Patient-reported pain data were collected with the use of a visual analog scale (at 2, 4, 12, and 20 hours postoperatively. Opiate use was measured and converted into parenteral morphine equivalents. The primary outcome was pain, and secondary outcomes included pain medication, antiemetic medication, and a quality of recovery questionnaire. Adverse effects were surveyed at 24 hours and 7 days. Concomitant procedures for urinary incontinence or pelvic organ prolapse did not preclude enrollment. RESULTS: Ninety women were randomly assigned consecutively at a single institution under the care of a fellowship-trained surgeon group. Demographics did not differ among the groups with mean age of 55 years, procedure time of 97 minutes, and prolapse at 51%. Postoperative pain scores were equivalent among both groups at each time interval. The belladonna and opium group used a mean of 57 mg morphine compared with 66 mg for placebo (P=.43) in 24 hours. Patient satisfaction with recovery was similar (P=.59). Antiemetic and ketorolac use were comparable among groups. Subgroup analyses of patients with prolapse and patients <50 years old did not reveal differences in pain scores. The use of belladonna and opium suppositories was uncomplicated, and adverse effects, which included constipation and urinary retention, were similar among groups. CONCLUSION: Belladonna and opium suppositories are safe for use after vaginal surgery. Belladonna and opium suppositories did not reveal lower pain or substantially lower narcotic use. Further investigation may be warranted to identify a population that may benefit optimally from belladonna and opium use.

Preoperative Belladonna and Opium Suppository for Ureteral Stent Pain: A Randomized, Double-blinded, Placebo-controlled Study.

OBJECTIVE: To investigate whether the use of a belladonna and opium (B&O) rectal suppository administered immediately before ureteroscopy (URS) and stent placement could reduce stent-related discomfort. METHODS: A randomized, double-blinded, placebo-controlled study was performed from August 2013 to December 2014. Seventy-one subjects were enrolled and randomized to receive a B&O (15 mg/30 mg) or a placebo suppository after induction of general anesthesia immediately before URS and stent placement. Baseline urinary symptoms were assessed using the American Urological Association Symptom Score (AUASS). The Ureteral Stent Symptom Questionnaire and AUASS were completed on postoperative days (POD) 1, 3, and after stent removal. Analgesic use intraoperatively, in the recovery unit, and at home was recorded. RESULTS: Of the 71 subjects, 65 had treatment for ureteral (41%) and renal (61%) calculi, 4 for renal urothelial carcinoma, and 2 were excluded for no stent placed. By POD3, the B&O group reported a higher mean global quality of life (QOL) score (P = .04), a better mean quality of work score (P = .05), and less pain with urination (P = .03). The B&O group reported an improved AUASS QOL when comparing POD1 with post-stent removal (P = .04). There was no difference in analgesic use among groups (P = .67). There were no episodes of urinary retention. Age was associated with unplanned emergency visits (P <.00) and "high-pain" measure (P = .02) CONCLUSION: B&O suppository administered preoperatively improved QOL measures and reduced urinary-related pain after URS with stent. Younger age was associated with severe stent pain and unplanned hospital visits.

Opium tincture versus methadone syrup in management of acute raw opium withdrawal: A randomized, double-blind, controlled trial.

The aim of this study was to evaluate the effectiveness of opium tincture versus methadone syrup in the management of acute withdrawal syndrome in opium dependent patients during the detoxification period. In this double-blind randomized controlled study, a total of 74 adult male raw opium dependent patients were treated with opium tincture or methadone syrup 2 times daily for 5 consecutive days. Detoxification was initiated by tapered dose reductions to reach abstinence. At the end of the 10th day, the medications were discontinued. The Objective Opioid Withdrawal Scale was used to assess withdrawal symptoms every day. Significant decreases on the Objective Opioid Withdrawal Scale were found for both treatment methods during the study period (p < .0001). However, there was no significant difference between groups on the total Objective Opioid Withdrawal Scale, and adverse effects existed. Opium tincture can be considered as a potential substitute for methadone syrup for suppression of raw opium withdrawal symptoms, with minimal adverse effects.

Mechanistic Population Pharmacokinetics of Morphine in Neonates With Abstinence Syndrome After Oral Administration of Diluted Tincture of Opium.

Conducting and analyzing clinical trials in vulnerable neonates are extremely challenging. The aim of this analysis is to develop a morphine population pharmacokinetics (PK) model using data collected during a randomized control trial in neonates with abstinence syndrome (NAS). A 3-compartment morphine structural PK model after intravenous (IV) administration from previously published work was utilized as prior, whereas an allometric scaling method with physiological consideration was used to extrapolate a PK profile from adults to pediatrics. The absorption rate constant and bioavailability were estimated in NAS after oral administration of diluted tincture of opium (DTO). Goodness-of-fit plots along with normalized prediction distribution error and bootstrap method were performed for model evaluation. We successfully extrapolated the PK profile from adults to pediatrics after IV administration. The estimated first-order absorption rate constant and bioavailability were 0.751 hour(-1) and 48.5%, respectively. Model evaluations showed that the model can accurately and precisely describe the observed data. The population pharmacokinetic model we derived for morphine after oral administration of DTO is reasonable and acceptable; therefore, it can be used to describe the PK and guide future studies. The integration of the previous population PK knowledge as prior information successfully overcomes the logistic and practical issue in vulnerable neonate population.

The pharmacology of medieval sedatives: the "Great Rest" of the Antidotarium Nicolai.

ETHNOPHARMACOLOGICAL RELEVANCE: Past practices of compound drugs from different plant ingredients enjoyed remarkable longevity over centuries yet are largely dismissed by modern science as subtherapeutic, lethal or fanciful. AIM OF THE STUDY: To examine the phytochemical content of a popular medieval opiate drug called the "Great Rest" and gauge the bioavailability and combined effects of its alkaloid compounds (morphine, codeine, hyoscyamine, scopolamine) on the human body according to modern pharmacokinetic and pharmacodynamic parameters established for these compounds. CALCULATIONS AND THEORY: We reviewed the most recent studies on the pharmacodynamics of morphine, codeine, hyoscyamine and scopolamine to ascertain plasma concentrations required for different physiological effects and applied these findings to dosage of the Great Rest. RESULTS: Given the proportional quantities of the alkaloid rich plants, we calculate the optimal dose of Great Rest to be 3.1±0.1-5.3±0.76 g and reveal that the lethal dose of Great Rest is double the therapeutic concentration where all three alkaloid compounds are biologically active. CONCLUSION: This study helps establish the effective dose (ED50), toxic dose (TD50) and lethal dose (LD50) rates for the ingestion of raw opium, henbane and mandrake, and describes their probable combined effects, which may be applied to similar types of pre-modern pharmaceuticals to reveal the empirical logic behind past practices.

Neglected role of hookah and opium in gastric carcinogenesis: a cohort study on risk factors and attributable fractions.

A recent study showed an association between hookah/opium use and gastric cancer but no study has investigated the relationship with gastric precancerous lesions. We examined the association between hookah/opium and gastric precancerous lesions and subsequent gastric cancer. In a population-based cohort study, 928 randomly selected, healthy, Helicobacter pylori-infected subjects in Ardabil Province, Iran, were followed for 10 years. The association between baseline precancerous lesions and lifestyle risk factors (including hookah/opium) was analyzed using logistic regression and presented as odds ratios (ORs) and 95% confidence intervals (CIs). We also calculated hazard ratios (HRs) and 95% CIs for the associations of lifestyle risk factors and endoscopic and histological parameters with incident gastric cancers using Cox regression models. Additionally, the proportion of cancers attributable to modifiable risk factors was calculated. During 9,096 person-years of follow-up, 36 new cases of gastric cancer were observed (incidence rate: 3.96/1,000 persons-years). Opium consumption was strongly associated with baseline antral (OR: 3.2; 95% CI: 1.2-9.1) and body intestinal metaplasia (OR: 7.3; 95% CI: 2.5-21.5). Opium (HR: 3.2; 95% CI: 1.4-7.7), hookah (HR: 3.4; 95% CI: 1.7-7.1) and cigarette use (HR: 3.2; 95% CI: 1.4-7.5), as well as high salt intake, family history of gastric cancer, gastric ulcer and histological atrophic gastritis and intestinal metaplasia of body were associated with higher risk of gastric cancer. The fraction of cancers attributable jointly to high salt, low fruit intake, smoking (including hookah) and opium was 93% (95% CI: 83-98). Hookah and opium use are risk factors for gastric cancer as well as for precancerous lesions. Hookah, opium, cigarette and high salt intake are important modifiable risk factors in this high-incidence gastric cancer area.