Biochemical responses as early and reliable biomarkers of organophosphate and carbamate pesticides intoxication: A systematic literature review.

Inhibition of cholinesterase (ChE) activity has been long considered as the main diagnostic method of organophosphate (OP) and carbamate pesticides poisoning; however, it has been shown that ChE activity may also be altered due to exposure to other non-organophosphorus toxicants and variety of different medical conditions. Hence, to avoid misdiagnosis, we aimed to systematically review available documents to look for additional biomarkers of OP and carbamate poisoning. The electronic databases in addition to Google scholar were searched for eligible articles on March 2022 using "organophosphate," "carbamate," and "biomarker" including all their similar terms. After collecting the relevant documents, the data were extracted and described qualitatively. In total, data of 66 articles from 51 human and 15 animal studies were extracted. Findings demonstrated that enzymes such as ß-glucuronidase, neuropathy target esterase, amylase, and lipase, in addition to hematological indicators such as CBC, CRP, lactate dehydrogenase, and CPK have high sensitivity and accuracy in the diagnosis of OP poisoning. Findings suggest that using various markers for diagnosis of OP intoxication is helpful for appropriate management, and early identifying the patients at risk of death. The suggested biomarkers also help to avoid misdiagnosis of OP poisoning with other similar conditions.

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.

Potential benefits versus hazards of herbal therapy during pregnancy; a systematic review of available literature.

The use of herbal medicine has considerably grown worldwide in the past two decades. Studies have shown that the prevalence of herbal diet therapy in pregnancy ranged from 1% to 60% in different societies. Many clinical reports have shown that some herbal medicines may have toxic effects on pregnant women and their fetuses because active ingredients of some medicinal plants can readily pass through the biological barriers (e.g., placental barrier). In the present study, we aimed to systematically review the literature to discover potential benefits versus the hazards of herbal therapy during pregnancy. For this purpose, a comprehensive literature review was performed, and after the literature search and selection of the appropriate documents, the desired data were extracted and reported. From 35 articles with a total of 39,950 study population, the results showed that some medicinal plants could cause severe toxicity on mothers and fetuses, in addition to abortion during pregnancy. It was also shown that some plants may lead to developmental abnormalities or fetal death. Findings of this survey showed that some herbal medicines have toxic, teratogenic, and abortive potential, particularly in the first trimester of pregnancy because active ingredients of some medicinal plants are able to pass through the placental barrier and reach the fetus.

Hematological Consequences of Valproic Acid in Pediatric Patients: A Systematic Review with a Mechanistic Approach.

PURPOSE: Although Valproate (VPA) has several advantages in controlling seizures, it may cause serious hematological consequences. Hematotoxicity of VPA is particularly important in pediatrics because patients at this age are at a growing risk of leukemia. For a conclusive agreement about the toxicity of VPA, in this study, we systematically reviewed the literature in which the hematological consequences of VPA had been emphasized. METHODS: A systematic literature search was performed in June 2021 on electronic databases to find original research on the association between VPA therapy and hematotoxicity in pediatric patients. For this purpose, the following search terms "hematotoxicity", "valproic acid" and "pediatrics" with different spellings and similar terms, were searched in the title, keywords, and abstracts of articles. The data were collected and used for qualitative data description. RESULTS: A total of 36 relevant articles with an overall 1381 study population were included. The results showed that VPA could cause severe hematotoxicity in children even at therapeutic doses. Neutropenia, thrombocytopenia, and bone marrow depression are the most common complications associated with VPA therapy. Also, findings showed that after discontinuation of VPA and starting other antiepileptic drugs or reducing the administered VPA dose, hematologic damages were entirely resolved, and all the hematological parameters improved during two weeks. CONCLUSION: This review showed that VPA therapy could cause hematotoxicity in children; hence, it is recommended to monitor hematological indices during VPA therapy. Also, according to the suggested mechanistic pathways of VPA side effects, a combination of VPA with antioxidants may reduce hematological side effects.

Heroin Intoxication Through Damaged Skin in a 7-Year-Old Girl.

Transdermal opioid intoxication has only been reported for pharmaceutical fentanyl and buprenorphine patches. Here, we report a rare case of heroin poisoning through damaged skin. A seven-year-old girl with an impaired level of consciousness and difficulty breathing was brought to a local hospital about one hour after burning with boiling water. She had a small second-degree burn on the right elbow. Clinicians were initially unable to obtain any reliable history from relatives about the cause of altered mental status. However, with a clinical suspicion of opioid poisoning, naloxone therapy started, and the patient was moderately improved. She underwent a coma workup; then she was referred to a tertiary care hospital. Further investigation revealed that after the burning, the mother left home to seek for a burn ointment from a neighbor, and the heroin-dependent father sprinkled some heroin powder over the burned area. Heroin was absorbed through the damaged skin and poisoned the child unintentionally. After three days of clinical management, the patient was discharged from the hospital in good condition without any complications. Heroin can be absorbed through damaged skin and cause poisoning. Diagnosis requires strong clinical suspicion, and an appropriate naloxone therapy may be life-saving.

Status of clinical toxicology education and ethics in medical care of poisoned patients in the Islamic Republic of Iran and a comparison with other countries.

Clinical toxicology is not recognized as a clinical speciality in Iran. After the chemical war gas attack by the Iraqi army against the Iranian troops in the 1980s, health professionals and Iranian authorities noticed the importance of this field in clinical medicine. Collaboration between the clinical toxicologists and toxicologists of pharmacy schools resulted in the establishment of the Iranian Society of Toxicology and Poisonings in 1991 and the National Board of Toxicology in 1993. Clinical toxicology fellowship was also formed as a joint collaboration between the toxicology and internal medicine boards in 2010. Medical doctors who specialized in clinical medicine are eligible to take the entrance examination of the fellowship. In spite of the advancement of clinical toxicology and increased number of acute poisonings and drug abuse, undergraduate teaching in this field is still lacking and being taught as part of the forensic medicine curriculum since 1952. There is a lack of an efficient national poison information and control centre (s) in Iran, and no action plan and practical efforts have been done for poisoning prevention. Therefore, the number of drug abuse and acute poisonings has increased over the past four decades and induced cultural, social and health problems. According to Iranian legal medicine organization reports, poisoning is the second-most occurring cause of unnatural death. The suicidal attempt is the most common method of acute poisoning in adults. Suicidal attempt including self-poisoning is not accepted in the Islamic point of view, and thus self-poisoning is mostly neglected and may not be treated appropriately in time in some regions of Iran. Accidental poisoning in children is also common in Iran and estimated to be between 20 000 and 25 000 cases annually over the recent years. In addition, social, cultural and economic problems have induced more health problems such as drug abuse and addiction even in children. Adulterated opium to lead for economic gaining has produced thousands of cases of lead poisoning over the past few years in nearly all opium addicts, which is still a major health problem in Iran. Ban on alcoholic beverages leads some people to make their own home-made spirits, which is unfortunately contaminated with methanol. Thousands of cases of methanol poisoning and even some epidemics have occurred over the past four decades in some parts of the country. Lack of availability of essential antidotes such as succimer and fomepizole has been a major problem for the effective treatment of poisoned patients. Despite the well-known fact that cases of poisoning and drug overdose constitute a significant proportion of hospital admissions in some developing countries, clinical toxicology education and medical care of the poisoned patients are lacking. Therefore, policymakers and health authorities should realize the importance of toxicology in clinical medicine. The Iranian Ministry of Health, medical care and Medical Education should implement clinical toxicology courses for medical students; establish effective national poisons information and control centres and advance clinical toxicology services for appropriate management of poisoned patients to improve public health and the overall health policy goals.

Effects of Methadone Maintenance Therapy on Thyroid Function of Adult Men.

One of the major challenges in methadone maintenance therapy (MMT) for drug dependence is the physiological side effects on endocrine hormones. Because of the key role of the thyroid gland in the normal functioning of the human body and brain, this study examined the effect of MMT on thyroid function. Thyroid hormones (T3, T4, and thyroid-stimulating hormone (TSH)) were evaluated in normal and user treated with MMT who were referred to the Province Clinical & Pathology Center of Urmia, Iran. The study was conducted for three months using the Case Series method. A total of 270 samples were collected, 215 were from individuals who were not treated, whereas 55 were from men treated with methadone. Average levels of T3 and T4 in non-treated sample of men are 1.34 ± 0.02 ng/mL and 90.96 ± 1.38 ng/mL while the corresponding values for patients treated with methadone are 1.39 ± 0.04 ng/mL for T3 and 94.57 ± 2.72 ng/mL for T4. Mean TSH levels of the non-treated group and the methadone consuming group were 1.75 ± 0.08 µIU/mL and 3.17 ± 0.45 µIU/mL, respectively. These results indicate that although men treated with methadone had higher levels of T3, T4, and TSH than normal individuals, only the difference in TSH level was significant. The importance of this difference among individuals on methadone maintenance programs should be investigated in larger samples over long periods of time. Additionally, the effects of methadone treatment on women should be examined.

Clinical features and prognosis of paraquat poisoning: a review of 41 cases.

PURPOSE: Paraquat is a contact herbicide which is highly toxic to human. Deliberate self-poisoning with paraquat continues to be a major public health concern in many developing countries. This study aimed to evaluate the data on cases of acute paraquat poisoning and to compare different variables between survivors and non-survivors. METHODS: In this cross sectional study, medical records of all paraquat intoxicated patients were reviewed at Taleghani hospital of Urmia, Iran, from 2007 to 2013, retrospectively. Demographics, clinical features and laboratory findings were evaluated. The variables compared between survivors and non-survivors were the amount of paraquat ingested, occurrence of vomiting after ingestion, time and place of hospital admission, length of hospital stay, leukocytosis, serum creatinine level and the outcomes. RESULTS: A total of 41 patients were evaluated. The mean ± standard deviation of patients' age were 31.6±16.9 years. The Length of hospital stay was 5.75±4.6 days. Most poisonings occurred in spring and summer. The in-hospital fatality rate was 46.3%. Statistically significant associations were found between the outcome of patients and the amount ingested (P=0.001), vomiting (P=0.004), early need to intensive cares (P=0.009), leukocytosis (P=0.001), serum creatinine levels (P=0.001), manifestations of acute hepatic (P<0.001) and respiratory failure (P=0.007). CONCLUSION: Ingestion of more than 30 ml, prompt vomiting, early need to intensive cares, leukocytosis, and multi-organ failures are major determinants for fatal outcome of paraquat poisoning. It may be useful to educate health professionals and the general population about the serious consequences of exposure to paraquat.

Comparison of prescribing indicators of academic versus non-academic specialist physicians in Urmia, Iran.

OBJECTIVE: As chief prescribers, physicians could have a key role in rational drug use. Core prescribing indicators of all physicians have been evaluated in the Islamic Republic of Iran for several years, but no study has assessed the effects of academic status of doctors on their prescribing behaviors. We aimed to compare prescribing indicators of two groups of academic and non-academic specialist physicians working in Urmia, Iran. METHODS: In this cross-sectional study, prescribing indicators of the total number of 37 academic and 104 non-academic specialist physicians in six medical specialties (infectious diseases, psychiatry, otorhinolaryngology, gynecology, pediatrics and general surgery) were studied during 2012 using Rx-analyzer, a dedicated computer application. A set of five quality indicators was used based on the World Health Organization and International Network for Rational Use of Drugs recommendations. FINDINGS: Totally, 709,771 medications in 269,660 prescriptions were studied. For academic and non-academic specialist physicians, the average number of medications per prescription was 2.26 and 2.65, respectively. Similarly, patients' encounters with injectable pharmaceuticals were 17.37% and 26.76%, respectively. The corresponding figures for antimicrobial agents were 33.12% and 45.46%, respectively. The average costs of every prescription were 6.53 and 3.30 United States Dollar for academic and non-academic specialist physicians, respectively. All the above-mentioned differences were statistically significant. CONCLUSION: Better prescribing patterns were observed in academic specialist physicians. However, they prescribed medications that were more expensive, while the reason was not investigated in this study. Further studies may reveal the exact causes of these differences.