Association of the OPRM1 variant rs1799971 (A118G) and clinical manifestations in tramadol poisoned patients: a cross-sectional study.

INTRODUCTION: The opioid receptor mu1 is a protein coding gene that can have different codes for a protein and may have variations (polymorphisms) affecting how opioids work. The aim of this study was to investigate the prevalence of the most common opioid receptor mu1 polymorphism (A118G) and any relationship between this polymorphism and features following tramadol overdose. MATERIALS AND METHODS: This was a cross-sectional study of patients admitted with tramadol poisoning to an Iranian hospital. These patients were not taking any other drugs or medications and had no history of seizures. RESULTS: The results showed that among the 83 patients included in the study, 57 (69 per cent) had the AA genotype, 25 (30 per cent) had the AG genotype, and one (1 per cent) had the GG genotype for the opioid receptor mu1 A118G polymorphism. Nausea and/or vomiting occurred in nine (11 per cent) patients and dizziness in 38 (46 per cent) patients. Serious adverse events included seizures in 51 (60 per cent) patients and respiratory failure requiring mechanical ventilation in 21 (25 per cent) patients. However, there was no significant association between the opioid receptor mu1 A118G polymorphism and these adverse events. DISCUSSION: In our study, the frequency of the A allele was greater than the G allele, and the AA genotype was more prevalent than AG. The GG genotype was the least common among the polymorphisms of opioid receptor mu1 rs1799971. There was no significant association between the opioid receptor mu1 A118G polymorphism and symptoms in tramadol-poisoned patients. Although these allele proportions are similar to the results reported in other Caucasian populations, they are dissimilar to the findings in Chinese and Singaporean populations. In these Asian studies, the predominant allele was the G allele. It has been suggested that a mutated G allele will decrease the production of opioid receptor mu1-related messenger ribonucleic acid and related proteins, leading to fewer mu-opioid receptors in the brain. CONCLUSIONS: This study found no significant association between the opioid receptor mu1 A118G polymorphism and adverse outcomes in tramadol-poisoned patients. However, more research is needed to draw more definitive conclusions due to the limited evidence and variability of opioid receptor mu1 polymorphisms in different populations.

Amelioration of pain and anxiety in sleep-deprived rats by intra-amygdala injection of cinnamaldehyde.

Background: Sleep disorders are accompanied by increased anxiety and somatic pain. In addition, it has been observed that anxiety and pain have a boosting effect on each other, resulting in continued sleep disturbances. Amygdala's (CeA) central nucleus plays a crucial role in these processes. Cinnamaldehyde (Cinn) is an aromatic compound with anti-anxiety, antioxidant, and sleep-promoting properties. The present study uses sleep-deprived rats to examine the effects of an intra-CeA injection of Cinn on pain and anxiety. Methods: Sleep deprivation (SD) was induced using the platform technique. 35 male Wistar rats were divided into five groups. Anxiety state and nociception were evaluated among groups using formalin test (F.T.), open field test (OFT), and elevated plus maze (EPM). Anxiety tests (OFT and EPM) were conducted in all groups. The first group was undergone FT without induction of SD (SD-FT+). The second group received SD without FT(SD+FT-). The third group received both SD and FT(SD+FT+). The treatment and vehicle groups have undergone both SD and FT in addition to the respectively intra-CeA injection of Cinn (SD+FT+ Cinn) and Cinn vehicle (SD+FT+ VC). The recorded behaviors were analyzed between groups using IBM SPSS 24th version. Results: SD did not lead to any significant difference in nociceptive behaviors in FT between groups SD-FT+ and SD+FT+ (P ≥ 0.05). At the same time, there was a considerable discrepancy in rearing behaviors (P < 0.006) and the number of fecal boli (P < 0.004) recorded in OFM between these groups. Treatment with Cinn led to decreased nociception (P < 0.038), decreased rearing behaviors (P < 0.01), and reduced defecation (P < 0.004) in group SD + FT+ Cinn in comparison to the group SD+FT+. There were no differences in anxiety test results between the first and second groups (P ≥ 0.05). Conclusion: SD can lead to elevated anxiety, while intra-CeA injection of Cinn ameliorated both perceptions of acute pain and anxiety. Besides, the conduction of FT before the anxiety test led to no disturbance in the results of anxiety tests.

Blood lead level evaluation in children presenting with chronic constipation in Tehran-Iran: a cross-sectional study.

Constipation is a common reason for children seeking medical care worldwide. Abdominal complaints and constipation are also common in lead-poisoned children. This study evaluates the prevalence of abnormal blood lead levels (BLL) among pediatric and adolescent patients and examines the association of constipation with elevated BLL. This was a prospective data collection of patients younger than 18 years old with the chief complaint of constipation seen in the Mofid Children's Hospital gastroenterology clinic and Loghman Hakim pediatric and pediatric gastroenterology clinics were eligible for enrollment in this study. Constipation was defined as infrequent or difficult defecation according to ROME IV criteria lasting 2 months or more. BLL was measured with a fresh capillary whole blood capillary sample. The LeadCare II device assays BLL using an electrochemical technique (anodic stripping voltammetry). A total of 237 patients were enrolled in the study. 122 (51.48%) were female and 115 (48.52%) were male. About one fifth of patients (49; 20.67%) had BLL ≥ 5 µg/dL. The mean BLL in the sample was 3.51 µg/dL. Abdominal pain was the most common symptom accompanying constipation (134; 56%). Multivariate analysis found endoscopic evaluation (P values 0.024, OR 3.646, 95% CI 1.189-11.178), muscle pain (P values 0.020, OR 24.74, 95% CI 1.67-365.83), and maternal education (P values 0.02, OR 4.45, 95% CI 1.27-15.57) with significant differences in groups of patients with normal and elevated BLL. Elevated BLL necessitates an assessment and plans to reduce childhood lead exposure. BLL screening in childhood constipation with refractory chronic abdominal pain may also eradicate the need for invasive procedures like endoscopic evaluation.

A cross-sectional multicenter linkage study of hospital admissions and mortality due to methanol poisoning in Iranian adults during the COVID-19 pandemic.

A methanol poisoning outbreak occurred in Iran during the initial months of coronavirus disease 2019 (COVID-19) pandemic. We aimed to evaluate the epidemiology of the outbreak in terms of hospitalizations and deaths. A cross-sectional linkage study was conducted based on the hospitalization data collected from thirteen referral toxicology centers throughout Iran as well as mortality data obtained from the Iranian Legal Medicine Organization (LMO). Patient data were extracted for all cases aged > 19 years with toxic alcohol poisoning during the study period from February until June 2020. A total of 795 patients were hospitalized due to methanol poisoning, of whom 84 died. Median [interquartile ratio; IQR] age was 32 [26, 40] years (range 19-91 years). Patients had generally ingested alcohol for recreational motives (653, 82.1%) while 3.1% (n = 25) had consumed alcohol-based hand sanitizers to prevent or cure COVID-19 infection. Age was significantly lower in survivors than in non-survivors (P < 0.001) and in patients without sequelae vs. with sequelae (P = 0.026). Twenty non-survivors presented with a Glasgow Coma Scale (GCS) score > 8, six of whom were completely alert on presentation to the emergency departments. The time from alcohol ingestion to hospital admission was not significantly different between provinces. In East Azerbaijan province, where hemodialysis was started within on average 60 min of admission, the rate of sequelae was 11.4% (compared to 19.6% average of other provinces)-equivalent to a reduction of the odds of sequelae by 2.1 times [95% CI 1.2, 3.7; p = 0.009]. Older patients were more prone to fatal outcome and sequelae, including visual disturbances. Early arrival at the hospital can facilitate timely diagnosis and treatment and may reduce long-term morbidity from methanol poisoning. Our data thus suggest the importance of raising public awareness of the risks and early symptoms of methanol intoxication.

An interrupted time series analysis of hospital admissions due to alcohol intoxication during the COVID-19 pandemic in Tehran, Iran.

The COVID-19 outbreak affected mental health globally. One of the major concerns following the COVID-19 pandemic was increased incidence of risky behaviors including alcohol consumption. This study evaluates the trend of alcohol poisoning in Loghman-Hakim Hospital (LHH), the main referral center of poisoning in Tehran, during the 2-year period from 1 year prior to 1 year after the onset (February 23rd, 2020) of the COVID-19 epidemic in Iran. All patients admitted with alcohol intoxication from February 23rd, 2019 to February 22nd, 2021 were evaluated and patient data extracted from LHH electronic hospital records. Alcohols were categorized as toxic (methyl alcohol) and non-toxic (ethyl alcohol). Of 2483 patients admitted, 796/14,493 (5.49%) and 1687/13,883 (12.15%) had been hospitalized before and after the onset of the COVID-19 epidemic in Iran, respectively. In total, 140 patients did not survive, of whom 131 (93.6%) were confirmed to have methanol intoxication. Mortality was significantly higher during the outbreak (127 vs 13; P < 0.001; OR: 4.90; CI 95%: 2.75 to 8.73). Among the patients, 503 were younger than age 20. Trend of alcohol intoxication showed increases in children (57 vs 17) and adolescents (246 vs 183) when compared before and after the COVID-19 epidemic outbreak. A total of 955 patients were diagnosed with methanol toxicity which occurred more frequently during the COVID-19 era (877 vs 78; P < 0.001; OR: 10.00; CI 95%: 7.75 to12.82). Interrupted time series analysis (April 2016-February 2021) showed that in the first month of the COVID-19 epidemic (March 2020), there was a significant increase in the alcohol intoxication rate by 13.76% (P < 0.02, CI = [2.42-24.91]). The trend of alcohol intoxication as well as resulting mortality increased in all age groups during the COVID-19 epidemic in Iran, indicating urgent need for the prevention of high-risk alcohol use as well as improved treatment.

Hospital-treated intentional self-poisoning events and in-hospital mortality in Tehran before and during the COVID-19 pandemic.

Hospital-treated intentional self-poisoning is common. The possibility of changed (increased) suicidal behaviors during the COVID-19 pandemic has been raised. To compare frequencies in self-poisoning events (SPEs) and the proportions with in-hospital mortality, in the year prior to and following the official onset of the COVID-19 pandemic, in a population of hospital-treated self-poisoning patients in Iran. All self-poisoned patients admitted to Loghman-Hakim Hospital, a clinical toxicology specialty hospital in Tehran, were included. The frequency of SPEs was compared between the one-year periods immediately before and after the onset of COVID-19 pandemic using Poisson regression. Differences in proportions of in-hospital mortality were also compared using logistic regression. A total of 14,478 patients with 15,391 SPEs (8,863 [61.2%] females) were evaluated in the study. There was no difference in the overall frequency of SPEs (relative risk [RR] of 0.99 [CI95% 0.96-1.03]), but a small increase in males (RR 1.07; 1.02-1.13) and a minor decrease in females (RR 0.95; 0.91-0.99). In total, 330 patients died (2.3% of all SPEs). There was no difference in overall in-hospital mortality odds ratio (OR: 0.98 [0.79-1.22]), in females (OR = 1.14 [0.80-1.60]) or males (OR = 0.92 [0.69-1.23]). There was no change in the frequency of SPEs and no difference in the in-hospital mortality proportions, suggesting that the COVID-19 pandemic had little or no effect on these aspects of suicidal behavior in Iran. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03248-y.

Trends of acute drug and chemical toxicities in adults and adolescents in Tehran, Iran between 2012 and 2018: a retrospective chart review.

Poisoning is among the top three common causes of suicidal deaths in Iran. We aimed to evaluate the epidemiologic trend of poisoning and its mortality rate in the largest tertiary toxicology referral center in Iran between 2012 and 2018. A total of 84,242 patients were hospitalized or died due to poisoning in this center during the study period, of whom 2114 (2.5%) died. The most frequent poisonings were those with antiepileptics, sedativehypnotics, and antiparkinson medications (T42) followed by narcotics and psychodysleptics (T40). Psychodysleptics had the highest mortality rate (684; 32.4% of the deaths). Among drugs of abuse, methadone was the most common cause of admission reported in 10,398 cases (12.3%). In conclusion, suicidal or recreational methadone poisoning is becoming the most common cause of admission to poisoning referral wards in Iran. Rigorous supervision of daily dosing at opioid maintenance clinics as well as efforts to control the black-market offering methadone are needed to prevent further methadone-related acute poisonings and deaths.

Blood lead concentrations among pediatric patients with abdominal pain: a prospective cross-sectional study.

BACKGROUND: Lead exposure is one of the most menacing of environmental exposures, particularly in children. Children are more susceptible to the effects of lead which manifest in many organ systems, including interference with mental and motor development. Lead poisoning can cause colicky abdominal pain. In this study, the authors sought to evaluate the prevalence of elevated blood lead level (BLL) and its contributing factors among pediatric patients presenting with abdominal pain. An epidemic of lead poisoning in adults was previously uncovered, and thus a concern for pediatric lead poisoning was raised. METHODS: Pediatric patients presenting to two pediatric clinics in Tehran with abdominal pain were eligible for enrollment in a descriptive prospective cross-sectional study. A predesigned questionnaire was filled for each patient by their consenting parents. The questionnaire queried demographic information, environmental, social, and other relevant parameters for lead exposure. After completion of the questionnaire, biometrics were obtained, and a blood sample was taken from each patient for measurement of BLL and complete blood count. RESULTS: A total of 187 patients were enrolled in the study. Of them, almost 20% had BLL ≥ 5 µg/dL. Univariate analysis showed that age (p = 0.002, OR 3.194, CI 95% 1.504-6.783), weight (p = 0.009, OR 2.817, CI 95% 1.266-6.269), height (p = 0.003, OR 3.155, CI 95% 1.443-6.899), and playing with both plastic and cotton toys (p = 0.03, OR 2.796, CI 95% 1.072-7.295) were significant predictors of high BLLs. Maternal level of education correlated with blood lead concentrations (p = 0.048, OR 2.524, CI 95% 1.006-6.331). CONCLUSIONS: A clinically significant number of cases of abdominal pain may have high BLLs. Specific attention should be paid to children presenting with abdominal pain, especially due to the detrimental effects of lead on their mental and motor development.

Prevalence of clinical and radiologic features in methanol-poisoned patients with and without COVID-19 infection.

AIM: The aim of the current study was to evaluate the prevalence of coronavirus disease (COVID-19) in methanol-poisoned patients admitted to two toxicology academic centers during the COVID-19 outbreak and determine their clinical features and chest/brain computed tomography (CT) findings. METHODS: Methanol-poisoned patients who had been referred during the COVID-19 pandemic were evaluated for signs and symptoms of COVID-19 by chest CT scans and/or polymerase chain reaction test. RESULTS: A total of 62 patients with confirmed methanol poisoning were enrolled in the study, with a median (interquartile range) age of 35 (28-44) years. Thirty-nine (62.9%) survived. Nine (14.5%) were diagnosed to have COVID-19, of whom four survived. There was a significant correlation between COVID-19 disease and a history of alcohol consumption (p = 0.036; odds ratio 1.7; 95% confidence interval, 1.3-2.2). Univariate analysis showed significant differences between infected and noninfected patients regarding their urea and time for first and second hemodialysis sessions, as well as the duration of ethanol administration. CONCLUSIONS: In conclusion, during the pandemic, specific attention should be paid to patients with a history of alcohol ingestion and elevated creatinine, loss of consciousness, and severe acidosis as these signs/symptoms could be present in both COVID-19 and methanol poisoning, making differentiation between the two challenging.

Lead poisoning; a neglected potential diagnosis in abdominal pain.

BACKGROUND: Abdominal pain may be a presenting symptom of lead poisoning and is often difficult to diagnose. This study aimed to determine the prevalence of abdominal pain in patients seen in the Laghman Hakim Hospital ED and GI clinic who were lead-intoxicated, with or without opiate use disorder. METHODS: Between July 2017 and January 2018, patients seen in the ED and GI clinic of Loghman Hakim Hospital with unexplained abdominal pain or abdominal pain resistant to treatment were enrolled. Informed consent was obtained from potential enrollees. For standardization, a pre-designed data collection tool was developed for uniform data acquisition. Opiate use was determined historically. For this study, lead poisoning was defined as a blood lead level (BLL) greater than or equal to 30 µg/dL (1.45 µmol/L) with concomitant GI symptoms. RESULTS: Of 125 patients admitted, 28 (22.4%) had BLLs higher than 30 µg/dL. None of the patients had signs and symptoms of opioid withdrawal syndrome during evaluation. Elevated BLLs were significantly correlated with oral opium use/abuse, history of addiction for over the preceding 12 years. The daily opium use was more than 2.75 g. There was a statistical correlation between lead toxicity and abdominal pain consistency and intensity, constipation, and paresthesias. Anemia, leukocytosis, and abnormal liver enzyme tests were laboratory findings associated with lead toxicity. Four patients died, one of whom was diagnosed with lead toxicity. CONCLUSION: Lead toxicity should be considered in the potential differential diagnosis of severe and resistant abdominal pain in patients referring to general EDs or GI clinics if a positive history of opium abuse exists.

Sudden Cardiac Arrest in an Asymptomatic Zinc Phosphide-Poisoned Patient: A Case Report.

Zinc phosphide is a gray to black powder mainly used as a rodenticide. In contact with gastric fluid, it releases phosphine which is the main toxic material of this compound. Phosphine interferes with oxidative respiratory cycle of the cells, but is generally expected to manifest its toxicity with prodromal signs and symptoms including abdominal pain, nausea and vomiting, metabolic acidosis, and increased liver function tests. A 64-year-old man was referred to our center with the history of ingestion of three full table spoons of zinc phosphide powder with only a mild GI discomfort. Abdominal X-ray revealed radiopaque material in epigastric and abdominal right upper quadrant. Despite treatment with polyethylene glycol and completely normal vital signs and lab tests, he experienced sudden cardiac arrest 19 h after admission. Autopsy showed clues of focal myopathy and fibrosis with evidences of ischemia and congestion in cardiac tissue, pulmonary edema, shrunken bilateral kidneys, and nutmeg yellow liver. Toxicology panel confirmed the presence of phosphine and zinc phosphide in the gastric fluid. The patient deteriorated suddenly despite being completely symptom-free during the hours preceding cardiovascular arrest. Since the cardiopulmonary injury is the most rampant cause of early death, checking of the cardiac enzymes and cardiac monitoring could be beneficial for early detection and efficient management of these patients.

Acute versus chronic methotrexate poisoning; a cross-sectional study.

BACKGROUND: Data is limited on comparison of acute and chronic methotrexate (MTX) poisoning. Methotrexate is an anti-folate drug that may be prescribed in some malignant or chronic inflammatory conditions. The aim of the current study was to compare signs and symptoms, complications, treatment and final outcome of acute and chronic MTX toxicity. METHOD: In a retrospective study in a referral center between March 2010 and March 2018, all patients who had been referred with the history of MTX poisoning and hospitalized due to acute or chronic poisoning were evaluated and compared. RESULTS: Of the total 27 patients admitted during the study period, 13 had referred with acute (group 1; consumption of MTX for less than 7 days) and 14 had referred with chronic toxicity (group 2; consumption of MTX for more than 7 days). Mean age was significantly higher in the second group (P < 0.001). Median total dose of MTX was similar between the groups (P = 0.90). Mucosal ulcers and skin lesions (P < 0.001 and 0.02, respectively) were the only symptoms significantly different between the two groups. Leukopenia (P < 0.001), thrombocytopenia (P < 0.001), and anemia (P = 0.04) were significantly more common in the second group. Blood urea nitrogen and creatinine were also significantly higher in the second group of the patients (P < 0.001 and P = 0.048). Median leucovorin administered dose was 200 mg [14, 480] versus 150 mg [75, 187] (P = 0.69) in groups 1 and 2, respectively. CONCLUSIONS: Chronic MTX poisoning is more serious than acute toxicity and accompanies higher dermatologic, hematologic, and hepatic complications necessitating more aggressive treatments including administration of higher doses of leucovorin or bone marrow stimulants such as G-CSF. This may be attributable to the underlying diseases and features (including older ages) which predispose these patients to complications.