Transgenerational Effects of Arsenic Exposure on Learning and Memory in Rats: Crosstalk between Arsenic Methylation, Hippocampal Metabolism, and Histone Modifications.

Arsenic (As) is widely present in the natural environment, and exposure to it can lead to learning and memory impairment. However, the underlying epigenetic mechanisms are still largely unclear. This study aimed to reveal the role of histone modifications in environmental levels of arsenic (sodium arsenite) exposure-induced learning and memory dysfunction in male rats, and the inter/transgenerational effects of paternal arsenic exposure were also investigated. It was found that arsenic exposure impaired the learning and memory ability of F0 rats and down-regulated the expression of cognition-related genes Bdnf, c-Fos, mGlur1, Nmdar1, and Gria2 in the hippocampus. We also observed that inorganic arsenite was methylated to DMA and histone modification-related metabolites were altered, contributing to the dysregulation of H3K4me1/2/3, H3K9me1/2/3, and H3K4ac in rat hippocampus after exposure. Therefore, it is suggested that arsenic methylation and hippocampal metabolism changes attenuated H3K4me1/2/3 and H3K4ac while enhancing H3K9me1/2/3, which repressed the key gene expressions, leading to cognitive impairment in rats exposed to arsenic. In addition, paternal arsenic exposure induced transgenerational effects of learning and memory disorder in F2 male rats through the regulation of H3K4me2 and H3K9me1/2/3, which inhibited c-Fos, mGlur1, and Nmdar1 expression. These results provide novel insights into the molecular mechanism of arsenic-induced neurotoxicity and highlight the risk of neurological deficits in offspring with paternal exposure to arsenic.

Extracorporeal treatment for ethylene glycol poisoning: systematic review and recommendations from the EXTRIP workgroup.

Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically, treatment of EG toxicity included supportive care, correction of acid-base disturbances and antidotes (ethanol or fomepizole), and extracorporeal treatments (ECTRs), such as hemodialysis. With the wider availability of fomepizole, the indications for ECTRs in EG poisoning are debated. We conducted systematic reviews of the literature following published EXTRIP methods to determine the utility of ECTRs in the management of EG toxicity. The quality of the evidence and the strength of recommendations, either strong ("we recommend") or weak/conditional ("we suggest"), were graded according to the GRADE approach. A total of 226 articles met inclusion criteria. EG was assessed as dialyzable by intermittent hemodialysis (level of evidence = B) as was glycolate (Level of evidence = C). Clinical data were available for analysis on 446 patients, in whom overall mortality was 18.7%. In the subgroup of patients with a glycolate concentration ≤ 12 mmol/L (or anion gap ≤ 28 mmol/L), mortality was 3.6%; in this subgroup, outcomes in patients receiving ECTR were not better than in those who did not receive ECTR. The EXTRIP workgroup made the following recommendations for the use of ECTR in addition to supportive care over supportive care alone in the management of EG poisoning (very low quality of evidence for all recommendations): i) Suggest ECTR if fomepizole is used and EG concentration > 50 mmol/L OR osmol gap > 50; or ii) Recommend ECTR if ethanol is used and EG concentration > 50 mmol/L OR osmol gap > 50; or iii) Recommend ECTR if glycolate concentration is > 12 mmol/L or anion gap > 27 mmol/L; or iv) Suggest ECTR if glycolate concentration 8-12 mmol/L or anion gap 23-27 mmol/L; or v) Recommend ECTR if there are severe clinical features (coma, seizures, or AKI). In most settings, the workgroup recommends using intermittent hemodialysis over other ECTRs. If intermittent hemodialysis is not available, CKRT is recommended over other types of ECTR. Cessation of ECTR is recommended once the anion gap is < 18 mmol/L or suggested if EG concentration is < 4 mmol/L. The dosage of antidotes (fomepizole or ethanol) needs to be adjusted during ECTR.

Chronic exposure to methadone induces activated microglia and astrocyte and cell death in the cerebellum of adult male rats.

Methadone is a centrally-acting synthetic opioid analgesic widely used in the methadone maintenance therapy (MMT) programs throughout the world. Considering its neurotoxic effects particularly on the cerebellum, this study aims to address the behavioral and histological alterations in the cerebellar cortex associated with methadone administration. Twenty-four adult male albino rats were randomized into two groups of control and methadone treatment. Methadone was subcutaneously administered (2.5-10 mg/kg) once a day for two consecutive weeks. The functional and structural changes in the cerebellum were compared to the control group. Our data revealed that treating rats with methadone not only induced cerebellar atrophy, but also prompted the actuation of microgliosis, astrogliosis, and apoptotic biomarkers. We further demonstrated that treating rats with methadone increased complexity of astrocyte processes and decreased complexity of microglia processes. Our result showed that methadone impaired motor coordination and locomotor performance and neuromuscular activity. Additionally, relative gene expression of TNF-α, caspase-3 and RIPK3 increased significantly due to methadone. Our findings suggest that methadone administration has a neurodegenerative effect on the cerebellar cortex via dysregulation of microgliosis, astrogliosis, apoptosis, and neuro-inflammation.

Dermatologic features of chronic intramuscular use of ketamine: a case report.

A 33-year-old female presented with lethargy due to multidrug toxicity. At physical examination, both gluteal regions showed brown patchy scars. The atrophic scars surrounding necrotic lesions were round and brown in appearance, and gluteal mass had gradually been lost. The patient disclosed using intramuscular ketamine injections for 3.5 years along with smoking hashish, alcohol use, intranasal use of methamphetamine (sniffing), and oral use of methadone. Since recreational drug use can affect multiple organs, dermatologists should be familiar with the dermatologic features of intravenous or intramuscular injecting drug use.

Diagnostic of Cytokeratin-19 Gene Expression in Iranian Breast Cancer Patients.

Sentinel lymph node (SLN) biopsy is currently the recommended procedure for axillary staging in clinically node-negative early breast cancer at diagnosis. The present study aimed to identify Cytokeratin-19 (CK19) gene profiles that accurately predicted the outcome of breast cancer patients. Fifty tumor samples from breast cancer patients were analyzed for the expression of the CK19 gene using quantitative PCR. Also, normal breast tissues (N = 50) were taken from the same patients that had undergone partial or total mastectomy. This gene signature was confirmed based on tumor's stage, grade, and estrogen receptor (ER) status, using conditional logistic regression. Based on these findings, the negative reported lymph nodes for metastasis had micrometastasis in significant values. There was a significant difference between normal and cancer samples in  CK19 expression. In this sentinel node evaluation, the relationship of this gene with tumor characteristics needs to be established and discussed finding a clear role for this gene in tumor outcome.

Diabetic ketoacidosis as a complication of methanol poisoning; a case report.

INTRODUCTION: Diabetic ketoacidosis (DKA) is a complication of diabetes presenting with high anion gap metabolic acidosis. Methanol poisoning, on the other hand, is a toxicology emergency which presents with the same feature. We present a case of methanol poisoning who presented with DKA. CASE PRESENTATION: A 28-year-old male was referred to us with blurred vision and loss of consciousness three days after ingestion of 1.5 L of an unknown mixture of bootleg alcoholic beverage. He had history of insulin-dependent diabetes and had neglected his insulin shots on the day prior to hospital admission due to progressive loss of consciousness. Vital signs were normal and venous blood gas analysis showed severe metabolic acidosis and a methanol level of 10.2 mg/dL. After eight hours of hemodialysis, he remained unresponsive. Diabetic ketoacidosis was suspected due to positive urine ketone and blood sugar of 411 mg/dL. Insulin infusion was initiated which was followed by full awakening and extubation. He was discharged completely symptom-free after 4 weeks. CONCLUSIONS: Diabetic ketoacidosis and methanol poisoning can happen simultaneously in a diabetic patient. Given the analogous high anion gap metabolic acidosis, physicians should pay particular attention to examination of the diabetic patients. Meticulous evaluation for both conditions is highly recommended.

Fatal overdose from injection of human growth hormone; a case report and review of the literature.

BACKGROUND: Human growth hormone (HGH) is a categorized as a performance-enhancing substance. HGH has been abused by athletes for doping purposes. CASE PRESENTATION: We present a first lethal case of HGH acute toxicity. A young-agitated-athlete with a history of somatropin for the past 2-year, who had hallucinations referred to the emergency department reporting to have abused of 300 mg subcutaneous injections of HGH. He was tachycardic with mild hypertension. Lab data revealed hypernatremia (157 mEq/L), hyperkalemia (5.3 mEq/L), high LDH (1448 U/L), and CPK (2620 U/L), in favor of rhabdomyolysis. Routine drug screening tests were negative for all substances. He was intubated due to low O2 saturation and progressive loss of consciousness. After several episodes of hyperthermia, hypertension, and possibly pulmonary embolism, he died subsequent to somatropin overdose. CONCLUSIONS: Complications of HGH misuse can be life-threatening and athletes should be warned of its deleterious effects.

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.

Fatal Outcome in Acutely Poisoned Children With Hospitalization: A 10-Year Retrospective Study From Tehran, Iran.

BACKGROUND: Acute poisoning is a significant and preventable cause of mortality among children internationally. The aims of this study were to assess the case fatality rate of children admitted to an inner-city hospital for acute poisoning and to compare the demographics and source of poisoning of fatal cases. METHODS: This was a retrospective review of patient data recorded in the Hospital Information System for Loghman Hakim Hospital, that is, the central referral hospital for poisoning in Tehran, Iran. We searched Hospital Information System for all admissions for poisoning in children (age, 0-12 years) over the 10-year period from March 2010 to March 2020, and all cases were included in the analysis. We determined the case fatality rate by dividing the number of fatal cases by the number of included cases. RESULTS: Of 8158 children admitted for poisoning, 28 cases (0.3%) died, among whom 19 (67.9%) were boys and 9 (32.1%) girls. The median age was 42 months, ranging from 2 to 144 months. Twenty-two cases (78.6%) were 0 to 5 years old. The most common cause of mortality in acute poisoning was methadone (n = 13, 46.4%), followed by raw opium (n = 5, 17.9%), aluminum phosphide, carbon monoxide, and wild mushrooms (n = 2 deaths each, 7.1%). Tramadol, colchicine, and petroleum accounted for 1 death each (3.6%). CONCLUSIONS: Mortality from unintentional poisoning disproportionately affects children younger than 5 years. Opioids (ie, methadone, opium, tramadol) accounted for two thirds of deaths in our sample. Our findings highlight the importance of educating parents that any toxic materials (licit or illicit) must be stored out of reach for children.

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.

Time-Dependent Changes in the Serum Levels of Neurobiochemical Factors After Acute Methadone Overdose in Adolescent Male Rat.

Acute methadone toxicity is a major public health concern which has adverse effects on brain tissue and results in recurrent or delayed respiratory arrest. Our study aimed to investigate the time-dependent changes in several serum biochemical markers of brain damage, spatial working memory, and the brain tissue following acute methadone overdose. Adolescent male rats underwent an intraperitoneal (i.p.) injection of 15 mg/kg methadone. In case of apnea occurrence, resuscitation was performed by a ventilatory pump and administrating naloxone (2 mg/kg; i.p.). The animals were classified into groups of treated rats; methadone and naloxone-Apnea (M/N-Apnea), M/N-Sedate, Methadone, Naloxone, and control (saline) groups. The serum levels of S100B, neuron-specific enolase (NSE), myelin basic protein factors, and (Lactate/Pyruvate) L/P ratio were evaluated at the time-points of 6, 24, and 48 h (h). We found that the alterations of S100B and L/P ratio were considerable in the M/N-Apnea and Methadone groups from the early hours post-methadone overdose, while NSE serum levels elevation was observed only in M/N-Apnea group with a delay at 48 h. Further, we assessed the spatial working memory (Y-maze test), morphological changes, and neuronal loss. The impaired spontaneous alternation behavior was detected in the M/N-Apnea groups on days 5 and 10 post-methadone overdose. The morphological changes of neurons and the neuronal loss were detectable in the CA1, striatum, and cerebellum regions, which were pronounced in both M/N-Apnea and Methadone groups. Together, our findings suggest that alterations in the serum levels of S100B and NSE factors as well as L/P ratio could be induced by methadone overdose with the presence or absence of apnea before the memory impairment and tissue injury in adolescent male rats.

COVID-19 pandemic and methanol poisoning outbreak in Iranian children and adolescents: A data linkage study.

BACKGROUND: During the first wave of COVID-19, many Iranians were poisoned by ingesting hand sanitizers and/or alcoholic beverages to avoid viral infection. To assess whether the COVID-19 pandemic resulted in an increased prevalence of accidental hand sanitizer/alcoholic beverage exposure in children and adolescents, we compared pediatric hospitalization rates during COVID-19 and the previous year. For poisoning admissions during COVID-19, we also evaluated the cause by age and clinical outcomes. METHODS: This retrospective data linkage study evaluated data from the Legal Medicine Organization (reporting mortalities) and hospitalization data from nine toxicology referral centers for alcohol-poisoned patients (age 0 to 18 years) for the study period (February 23 to June 22, 2020) and the pre-COVID-19 reference period (same dates in 2019). RESULTS: Hospitalization rates due to ethanol and methanol exposure were significantly higher in 2020 (n = 375) than 2019 (n = 202; OR [95% CI] 1.9 [1.6, 2.2], p < 0.001). During COVID-19, in patients ≤15 years, the odds of intoxication from hand sanitizers were significantly higher than from alcoholic beverages, while in 15- to 18-year-olds, alcoholic beverage exposure was 6.7 times more common (95% CI 2.8, 16.1, p < 0.001). Of 375 children/adolescents hospitalized for alcoholic beverage and hand sanitizer exposure in 2020, six did not survive. The odds of fatal outcome were seven times higher in 15- to 18-year-olds (OR (95% CI) 7.0 (2.4, 20.1); p < 0.001). CONCLUSION: The Iranian methanol poisoning outbreak during the first wave of COVID-19 was associated with significantly increased hospitalization rates among children and adolescents-including at least six pediatric in-hospital deaths from poisoning. Public awareness needs to be raised of the risks associated with ingesting alcoholic hand sanitizers.

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.

Protective effect of flumazenil infusion in severe acute benzodiazepine toxicity: a pilot randomized trial.

OBJECTIVE: We aimed to investigate the efficacy of flumazenil infusion in the maintenance of arousal and prevention of development of complications in severe benzodiazepine poisoning. MATERIALS AND METHOD: Sixty severely poisoned patients (intubated due to loss of consciousness) intoxicated by sole benzodiazepines referred to Loghman Hakim hospital between May 2018 and August 2019 were considered to be included in the current study. All were evaluated for possible contraindications of flumazenil administration. If there were no contraindications, we continued supportive care in one group and supportive care plus flumazenil infusion in the second group. Following response to the stat dose of flumazenil, complications, hospital stay, and outcome were compared between these two groups. RESULTS: A total of 60 benzodiazepine-poisoned patients aged between 16 and 84 years old (37 males and 23 females) were enrolled. There was no statistically significant difference between these two groups regarding the period of hospital stay. Need for intubation significantly decreased in the infusion group. None of the patients experienced seizure or dysrhythmia. One patient died in the control group which received only a stat dose of flumazenil. CONCLUSIONS: Administration of flumazenil is safe in benzodiazepine-poisoned patients with appropriate indications. Flumazenil infusion can significantly decrease the need for intubation and subsequent ICU admission. Even though flumazenil is an expensive antidote, its administration may decrease the need for ICU beds in the setting of acute poisoning.

Environmental assessment of pediatric Lead exposure in Tehran; a prospective cross-sectional study.

BACKGROUND: Ingestion and inhalation are common routes of exposure for lead in humans. Developing countries still have unacceptably high rates of lead toxicity, especially in children. Studies on probable risk factors of lead poisoning in Iranian children are insufficient. In this study, we aimed to evaluate possible environmental factors in children with high blood lead concentrations living in Tehran and neighboring cities. METHODS: In a prospective cross-sectional study between March 2018 and March 2019 we followed all children referred from two pediatric gastrointestinal clinics with blood lead level (BLL) > 5 µg/dL in metropolitan Tehran to investigate possible environmental risk factors in their home. Household specimens including scratched wall paint, house floor dust, windowsill dust, tap water, and consumed spice were evaluated using atomic absorption method to detect lead concentrations. Epidemiological and environmental data collected through in-depth interviews with parents/guardians. Industrial areas were defined based on municipality maps on industrial places. RESULTS: Thirty of 56 parents/guardians with BLL > 5 µg/dL agreed to be followed through environmental investigation. The only categorical statistically significant risk factor was a history of lead poisoning in the family and living in an industrial zone. There was a positive correlation between BLL and interior windowsills dust lead level, r = 0.46, p = 0.01. Scratched paint lead level and BLL showed a significant positive correlation, r = 0.50, p = 0.005. House floor dust lead level (median = 77.4, p < 0.001) and interior windowsill dust lead level (median = 291, p = 0.011) were both significantly higher than the environmental protection agency (EPA) standards of 40 µg/ft2, 250 µg/ft2. Interior windowsill dust lead concentrations were significantly higher in industrial areas (p = 0.026). CONCLUSION: Children's playing environment should be cleaned more often to reduce dust. Moreover, specific rules may need to be implemented for paint lead concentrations and air pollution, especially in industrial areas.

Encephalopathy following ingestion of Lead-contaminated opium; magnetic resonance imaging findings.

BACKGROUND: Encephalopathy is an uncommon but serious presentation of lead toxicity. OBJECTIVE: We aimed to determine and follow-up the brain magnetic resonance imaging (MRI) abnormalities in the patients with lead encephalopathy due to ingestion of lead contaminated opium. METHODS: In a cross-sectional study during lead-contaminated opium outbreak, all lead-poisoned patients with any signs/symptoms of encephalopathy were included. RESULTS: Of 19 patients with lead encephalopathy, five died early and other five could not be sent to MRI during their hospitalization period. Mean age was 51 ± 11 years and males were dominant (89%). Median [IQR] blood lead level (BLL) was 101 [81, 108] µg/dL (range; 50 to 200 µg/dL). There was no correlation between MRI findings and signs/symptoms. MRI was normal in six and abnormal in three. Bilateral symmetric involvement of parieto-occipital lobes was observed. Gray matter, gray-white matter junction, and subcortical white matter were also affected. Follow-up MRI was performed in two with abnormal MRI which showed complete and near complete resolution of the abnormalities after cessation of opium use and treatment. CONCLUSION: There was no correlation between MRI findings and BLL. Complete recovery of brain MRI lesions was detected after cessation of opium use.

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.

Atypical presentation of COVID-19; an observational retrospective study.

BACKGROUND: COVID-19 infection may present with atypical signs and symptoms and false negative polymerase chain reaction (PCR) tests predisposing healthy people and health care workers to infection. The aim of the current study is to evaluate the features of atypical presentations in COVID-19 infection in a referral center in Tehran, Iran. METHODS: Hospital database of inpatients admitted to Loghman Hakim hospital between February 20th and May 11th, 2020 was reviewed and all patients with final diagnosis of COVID-19 infection were evaluated for their presenting symptoms. Patients with chief complaints of "fever", "dyspnea", and/or "cough" as typical presentations of COVID-19 were excluded and those with other clinical presentations were included. RESULTS: Nineteen patients were included with a mean age of 51 ± 19 years, of whom, 17 were males (89%). Median [IQR] Glasgow coma scale (GCS) was 14 [13, 15]. Almost 10 had referred with chief complaint of methanol poisoning and overdose on substances of abuse. Only 8 cases (42%) had positive COVID-19 test. Nine (47%) needed invasive mechanical ventilation, of whom, two had positive COVID-19 test results (p = ns). Eight patients (42%) died with three of them having positive PCRs. CONCLUSIONS: In patients referring to emergency departments with chief complaint of poisoning (especially poisonings that can result in dyspnea including substances of abuse and toxic alcohols), gastrointestinal, and constitutional respiratory symptoms, attention should be given not to miss possible cases of COVID-19.

Buprenorphine to reverse respiratory depression from methadone overdose in opioid-dependent patients: a prospective randomized trial.

BACKGROUND: Naloxone is the usual drug used in opioid-induced respiratory depression but it has a short half-life, precipitates withdrawal in dependent patients, and thus for persistent reversal of long-acting opioids has to be given by titrated doses and infusions. The partial agonist buprenorphine has a much longer duration of action and causes less severe withdrawal, but still should largely reverse respiratory depression induced by full agonist opioids. We aimed to compare the efficacy/safety of buprenorphine and naloxone in reversing respiratory depression in methadone-poisoned opioid-dependent patients. METHODS: Patients with methadone-induced respiratory depression were randomized to receive naloxone (titrated doses), or lower or higher doses of buprenorphine (10 µg/kg or 15 µg/kg). The primary outcome was immediate reversal of respiratory depression. We also recorded acute opioid withdrawal, need for intubation/recurrent apnea, repeated doses of opioid antagonists, length of hospital stay, other morbidity, and mortality. The study was registered with the Iranian Registry of Clinical Trials (Trial ID: 18265; Approval code: IRCT2015011020624N1). RESULTS: Eighty-five patients were randomized; 55/56 patients who received buprenorphine had rapid reversal of respiratory depression, which persisted for at least 12 h. Naloxone was effective in 28/29 patients, but often required very high titrated doses (thus delaying time to respond) and prolonged infusions. Intubation (8/29 vs 5/56) and opioid withdrawal (15/29 vs 7/56) were less common with buprenorphine. There were no serious complications or deaths in those receiving buprenorphine. The 15-µg/kg buprenorphine dose appeared to provide a longer duration of action, but precipitated withdrawal more frequently than the 10-µg/kg dose. CONCLUSION: Buprenorphine appears to be a safe and effective substitute for naloxone in overdosed opioid-dependent patients. Further studies are warranted to explore the optimal dosing strategy for buprenorphine to consistently maintain reversal of respiratory depression but not precipitate withdrawal. TRIAL REGISTRATION NUMBER: IRCT2015011020624N1. Registered 30 September 2015.

Methadone-induced encephalopathy: a case series and literature review.

BACKGROUND: Accidental ingestion or consumption of supra-therapeutic doses of methadone can result in neurological sequelae in humans. We aimed to determine the neurological deficits of methadone-poisoned patients admitted to a referral poisoning hospital using brain magnetic resonance (MR) and diffusion weighted (DW) imaging. METHODS: In this retrospective study, brain MRIs of the patients admitted to our referral center due to methadone intoxication were reviewed. Methadone intoxication was confirmed based on history, congruent clinical presentation, and confirmatory urine analysis. Each patient had an MRI with Echo planar T1, T2, FLAIR, and DWI and apparent deficient coefficient (ADC) sequences without contrast media. Abnormalities were recorded and categorized based on their anatomic location and sequence. RESULTS: Ten patients with abnormal MRI findings were identified. Eight had acute- and two had delayed-onset encephalopathy. Imaging findings included bilateral confluent or patchy T2 and FLAIR high signal intensity in cerebral white matter, cerebellar involvement, and bilateral occipito-parietal cortex diffusion restriction in DWI. Internal capsule involvement was identified in two patients while abnormality in globus pallidus and head of caudate nuclei were reported in another. Bilateral cerebral symmetrical confluent white matter signal abnormality with sparing of subcortical U-fibers on T2 and FLAIR sequences were observed in both patients with delayed-onset encephalopathy. CONCLUSIONS: Acute- and delayed-onset encephalopathies are two rare adverse events detected in methadone-intoxicated patients. Brain MRI findings can be helpful in detection of methadone-induced encephalopathy.