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The Arum palaestinum plant is one of the 26 species of the Arum genus of the Araceae family. This plant species is found through the Mediterranean region, Western Asia, and Europe. The leaves and seeds of the plant contain needle-shaped oxalate crystals that can irritate the affected tissue (skin, oral cavity, or GI tract) upon exposure. Up to this date, there is no available literature supporting the epidemiology or the clinical manifestations of poisoning by this plant. We retrospectively reviewed all Arum palaestinum exposures to children younger than 18 years of age reported to the Israel National Poison Information Center during 2017 from the IPIC computerized data system. We extracted demographic data and clinical data from those digital files. We reviewed the files of 53 patients' files and found slight male predominance (58% vs. 42%), and the age of exposure ranged from 9 month to 15 years. The main site of exposure was at home in most cases (47%) followed by outdoor exposure in 40% of the cases. In 66% of the cases, minor clinical manifestations were reported, mainly erythema and mouth irritation, agitation, and drooling. Asymptomatic patients composed 34% of the cases. In 17% of the cases, patients were recommended to visit an ambulatory facility, and other 15% of the cases were referred to the emergency department. There were no cases of severe poisoning, upper airways compromise, or death.Conclusion: Poisoning by Arum palaestinum is one of the most common pediatric plant poisoning in Israel. Our study supports with clinical data for the first time that this poisoning is self-limited, confined to the affected mucosa, and most likely does not necessitate any intervention. What is Known • A. palaestinum poisoning is one of the most common pediatric plant poisoning in Israel. • The leaves and seeds of the plant contain needle-shaped oxalates crystals. What is New • Pediatric exposure to A. palaestinum usually causes only mild and self-limited poisoning. • Expectant observation is the preferred management of such exposure.

Most calls to poison information centers are from the public, pertaining to young children, and due to minor or nontoxic exposures. Rational poison center consultations can prevent unnecessary visits to emergency departments (EDs), callers’ adherence to such advice is required. Estimate adherence of callers from the public to the poison center concerning exposures of young children to the advice provided by the clinical toxicologist, estimate the number of unnecessary ED visits of these children prevented by poison center consultations. Prospective, phone-survey cohort study. Calls from the public concerning children under 6 years old were recorded and collected, telephone follow-up was performed within two weeks. Data collected included: demographics, exposure, severity, triage advised, adherence to the advice, reasons for nonadherence, and what the caller would have done had the poison center been unavailable. The study was conducted over 3 months representing different seasons and holidays times during a 1-year period. 1762 callers completed the telephone follow-up; 1443 (81.9%) cases were asymptomatic at the time of call; 1452 (82.3%) were advised to remain at home, 175 (9.9%) and 137 (7.8%) were referred to community clinics and EDs, respectively; 1648 (93.5%) of callers adhered to the advice provided; highest adherence rate was among callers advised to stay home (98.3%, 1427), and 78.9% (108) and 62.1% (109) among callers referred to EDs and community clinics, respectively. Among callers advised to stay home, 491 stated that they would have referred themselves to the ED had the poison center been unavailable, an annual estimate of 4309 cases. The main parameter predicting nonadherence was calls made during night shift. The high adherence of callers to the poison center consultation suggests it plays an important role in preventing unnecessary ED visits of young children due to poison exposures, and may substantially reduce ED load and costs.

Introduction One session of water-pipe tobacco smoking (WPS) can increase carboxyhemoglobin (COHb) to levels comparable to those reported in carbon monoxide poisoning, which may cause memory impairment and confusion. Methods A prospective study evaluating healthy volunteers pre- and post-30 min of WPS session. Primary outcome parameters were executive cognitive measures [digit span test and Paced Auditory Serial Addition Test (PASAT)]. The effect of repeated cognitive testing 30 min apart without WPS was evaluated in age- and sex-matched healthy volunteers. Secondary outcome parameters included cardio-pulmonary, COHb, serum nicotine, and cytokine changes. Results Thirty-five subjects aged 25.6 ± 4.5 years smoked water-pipe for a 30-min session. Control group included 20 subjects aged 25.2 ± 5.1 years. Digit span test median score decreased after WPS (16 and 15, respectively, p = .003), insignificant decrease in controls. Median PASAT score increased after WPS (49 and 52, respectively, p = .009); however, a much larger significant increase was observed in controls (p ≤ .001). One WPS session resulted in significant increases in heart and respiratory rates and significant decrease in FEF25–75%. Post WPS, median COHb levels increased (from 2.2% to 10.7%, p < .0001) as did median serum nicotine levels (from 1.2 to 26.8 ng/mL, p < .0001). Serum cytokines levels: IL-2 and IL-6 increased (p < .0001 for each), and IL-10 and IL-5 decreased (p < .0001 and p = .04, respectively). Conclusions One session of WPS resulted in significant negative effects on cognitive executive measures, significant increases in COHb and serum nicotine levels, and significant changes in serum cytokines. Our findings call for increasing awareness towards the possible consequences of cognitive alterations following a 30-min session of WPS. Implications One 30-min session of water-pipe smoking resulted in negative effects on executive cognitive measures, increased carboxyhemoglobin and serum nicotine, and significant changes in serum cytokine levels. This study adds to the accumulating evidence on the harmful effects of water-pipe smoking, a growing epidemic, and calls for awareness of its possible consequences of acute cognitive alterations.

During pregnancy and breastfeeding, many women require prescription medications. Concerns about drug effects on the fetus or breastfed infant may lead to decreased adherence. Our objective was to evaluate the adherence of pregnant and breastfeeding Israeli women to prescription drugs, the information they received regarding drug safety, and the women's awareness and pattern of the use of Teratogen Information Services (TIS) in Israel.We conducted a prospective observational cohort study among pregnant and breastfeeding women who had contacted the Israel Poison Information Center (IPIC) to consult about prescription medications. In a follow-up telephone call, we assessed adherence (defined as medication initiation by the time of the follow-up call) and the patients' recollection of the safety information given by the prescribing physician. In an additional cohort of post-partum women, we assessed their awareness about TIS in Israel.We included 59 pregnant women (62 prescriptions), 75 breastfeeding women (80 prescriptions), and 49 postpartum women. About two-thirds of all prescriptions were for antimicrobial drugs. By the time of the follow-up call, most participants (89% of pregnant and 89% of breastfeeding women) had initiated medications. Eight (11%) breastfeeding women stopped breastfeeding their babies while using the medication. Patients reported receiving explicit and unequivocal information concerning medication safety by the prescriber for 50% and 55% of prescriptions to pregnant and breastfeeding women, respectively. 70% of postpartum women interviewed in the maternity ward were not aware of TIS in Israel.We observed high adherence rate to prescription medication therapy among pregnant and breastfeeding women in our cohort. Only about half of the women reported receiving comprehensive drug safety information by the prescriber. Raising awareness of the importance of medication safety counseling among both physicians and patients may contribute to the quality of medical care of pregnant and breastfeeding women in Israel.

The Mediterranean region is, by far, a prime travel destination, having hosted more than 330 million tourists in 2016, mostly for seaside holidays. A greatly increased influx of thermophilic Red Sea species, introduced through the Suez Canal in a process referred to as Lessepsian invasion (in honor of Ferdinand de Lesseps who instigated the building of the Suez Canal), have raised awareness among scientists, medical personnel, and the public, of health risks caused by some venomous and poisonous marine species. The main species of concern are the poisonous Lagocephalus sceleratus, and the venomous Plotosus lineatus, Siganus luridus, Siganus rivulatus, Pterois miles, Synancea verrucosa, Rhopilema nomadica, Macrorhynchia philippina and Diadema setosum. Recognizing that the main factors that drive the introduction and dispersal of Red Sea biota in the Mediterranean, i.e., Suez Canal enlargements and warming seawater, are set to increase, and international tourist arrivals are forecasted to increase as well, to 500 million in 2030, an increase in intoxications and envenomations by alien marine species is to be expected and prepared for.

Plotosus lineatus is a venomous fish that has migrated from the Indo-Pacific region to the Mediterranean Sea (Lessepsian migrant). Its presence in the Mediterranean Sea was first recorded in 2002 and was observed in growing schools. Its spines contain toxins with lytic, hemolytic and edematous activities.To characterize the injuries caused by Plotosus lineatus in the Southeastern Mediterranean Sea.A prospective observational case series of consultations provided by a national Poison Center pertaining to Plotosus lineatus from 2007 to 2016. Demographic and clinical data and method of fish identification were retrieved from the medical toxicological records, and described.Eighty four cases were included; the main findings are: median age 35 (range 3-80) years, 91.7% males, 51.2% fishermen, 78.6% palm injuries, 94% and 4.8% were mildly and moderately injured, respectively. Main local manifestations included pain, puncture wound, swelling, and erythema (90.5%, 70.2%, 33.3%, and 16.7%, respectively). Systemic signs were minor and infrequent (≤7.1%), including hypertension, tachycardia, vomiting, chills, and weakness. Management included wound disinfection, immersion in hot water, tetanus prophylaxis, and analgesics. No patient required hospital admission. The fish was identified mostly by the victim with the aid of the Poison Center (mainly by typical description, and a picture), and some by marine biologists.Plotosus lineatus is a new fish in the Southeastern Mediterranean Sea. It affects fishermen handling fishing nets, and beach hikers stepping on or holding it. Injuries caused by its spines usually result in minor effects; pain may be intense. Treatment includes disinfection, analgesics, and antitetanus and antibiotics as needed. No lethal cases were recorded, unlike exposure of animals to the venom of the Indo-Pacific species; reason is unclear. Our series illustrates the consequences of manmade disruption of ecosystem resulting in invasion of toxic species to a new environment, affecting human health.

BACKGROUND Therapeutic drug monitoring (TDM) for busulfan supports dose adjustment during conditioning for stem cell transplantation. The authors aimed to develop and validate limited sampling strategies (LSS) of 4-5 samples for a precise estimation of the area under concentration (AUC)-time curve of busulfan, in plasma as an alternative to an intensive sampling strategy (ISS) requiring 9-10 samples. METHODS ISS TDM data from 297 patients (≤18 years of age) were used. AUCLSS was calculated using the trapezoidal rule and multiple linear regression (MLR). Unlike more complex modeling methods, MLR does not require sophisticated software or advanced training of personnel. MLR coefficients were estimated in the development subset containing randomly selected 50% of the records and were then used to calculate the AUCLSS of the remaining records (the validation subset). The agreement between dose adjustment recommendations (DAR) based on ISS and LSS, in the validation subset, was evaluated by a Bland-Altman analysis. A DAR deviating from an ISS-based reference by

The Israel Poison Information Center (IPIC), Rambam Health Care Campus, provides 24-hour telephone consultations on clinical toxicology and drug and reproductive toxicology. It participates in research, teaching and regulatory activities, and provides laboratory services. In 2014, nurse specialists in poison information joined the IPIC.To report the epidemiology of poison exposures in Israel.We present computerized queries and a descriptive analysis of the medical records database of the IPIC for 2017.A total of 39,928 poison exposure cases were recorded, reflecting increases of 226.3% and 26.7% compared with 1995 and 2012, respectively. Children6 years of age were involved in 47.0% of cases; 80.4% of calls were made by the public and 17.8% by physicians; 74.2% of exposures were unintentional and 7.3% intentional. Pharmaceuticals were involved in 51.4% of cases, chemicals in 36.9%, bites and stings in 2.2%, and plants and mushrooms in 1.5%. Substances most frequently involved were analgesics, cleaning products, and antimicrobials. Clinical severity was moderate/major in 3.3%, mainly due to insecticides, drugs of abuse, and corrosives. Three fatalities were recorded (due to colchicine, organophosphates, and volatile substance inhalant abuse).Poison exposures and poisonings have markedly increased in Israel, contributing substantially to morbidity. The IPIC prevented unnecessary referrals to emergency departments. Its database is a valuable national resource for collecting and monitoring poisoning exposure cases. It can be used as a real-time surveillance system for the benefit of public health. It is recommended that reporting to the IPIC become mandatory, and its activities adequately supported by national resources.

The unmonitored use of herbal medicinal remedies by patients with cancer presents a significant challenge to oncology healthcare professionals. We describe an increasingly popular herbal “wonder drug,” Ephedra foeminea (Alanda in Arabic), whose use has spread from the Palestinian patient population throughout the Middle East. We conducted a multicentered and multidisciplinary collaborative research effort in order to understand the potential benefits and harms of this popular herbal remedy. We conducted an in-depth search of the medical literature, both traditional and modern, for any mention of the clinical use of Alanda for the treatment of cancer. We then tested the remedy, first for toxic ephedra alkaloid components and then for anticancer effects, as well as effects on the cytotoxic activity of chemotherapy agents (cisplatin and carboplatin) on breast cancer cell cultures. We found no mention in the literature, both conventional and traditional, on the use of Alanda for the treatment of cancer. Laboratory testing did not find any toxic components (i.e., ephedra alkaloids) in the preparation. However, in vitro exposure to Alanda led to a reduced cytotoxic effect of chemotherapy on breast cancer cell cultures. The use of an integrative ethnobotanical, laboratory and clinical research-based approach can be extremely helpful when providing nonjudgmental and evidence-based guidance to patients with cancer, especially on the use of traditional herbal medicine. The effectiveness and safety of these products need to be examined by integrative physicians who are dually trained in both complementary medicine and supportive cancer care.

Background Increasing use of cannabis for medical and recreational purposes has augmented concerns about associated poisoning, and specifically pediatric and adolescent poisonings. Synthetic cannabinoids, often marketed as cannabis replacement, have recently emerged and knowledge and awareness of their toxic effects is growing. The objective of this study was to characterize and compare cannabinoid poisonings (medical and recreational cannabis, and synthetic cannabinoids) in Israel during the period 2007–2018. Methods The three types of cannabinoid exposures reported to the Israel Poison Information Center (IPIC) between 2007 and 2018 were identified. Differences in distribution of the three types of agents with respect to demographic and clinical factors were examined using univariate statistics, and time trends were plotted. Results Out of the total 615 poison-exposure cases identified, 55% were recreational cannabis cases, 33% were synthetic cannabinoid cases and 12% were medical cannabis cases. Compared to recreational cannabis exposures, synthetic cannabinoid exposures were more likely to be male, to have both gastrointestinal and cardiovascular manifestations and less likely to be called in by the public as opposed to called in by health care professionals and less likely to be treated on-site. Medical cannabis exposures were less likely to be male, more likely to be called in by the public, less likely to present with co-use of other substances and more likely to have gastrointestinal manifestations. Throughout the study period an increase in exposure cases were observed for medical and recreational cannabis cases, whereas synthetic cannabinoid cases showed an increase until 2014 and then a steep decrease. Conclusions Despite the low toxicity of different types of cannabinoids, training of physicians and other health care professionals related to cannabinoid poisoning is important. This is particularly important in jurisdictions where legal access to cannabis is becoming increasingly available.

A 70-year-old woman suffered severe irritation in her oral cavity after biting Dieffenbachia amoena petiole. She was treated a few hours after the exposure with systemic and local analgesics, as well as with systemic first generation antihistamine, and her symptoms improved rapidly. Dieffenbachia is a common household plant that contains oxalate raphides which cause irritation and microtrauma. Injuries are caused by exposure through the mouth, and also by contact with eyes or skin. Clinical presentation is dependent on the route of exposure. It includes pain and edema in the oral cavity following biting the leaves or the stem of the plant. Direct oral contact with the plant juice can also cause symptoms. There are some case reports of severe injuries that caused oro-pharyngeal inflammation and edema, with impending obstruction of the upper airways. Treatment includes respiratory support. Water or milk can be given to alleviate oral and throat irritation; some clinicians recommend first generation antihistamines. It should be noted that treatment recommendations are based on reports, not on clinical trials.

Liquid chromatography with mass spectrometry (LC-MS/MS) is the method of choice for the determination of everolimus whole blood concentrations but is not always available. Therefore, immunoassays have been developed for clinical monitoring of everolimus. In previous studies, the Quantitative Microsphere System (QMS) immunoassay had a positive bias compared with LC-MS/MS, but was judged acceptable, although clinical agreement (eg, 95% limits of agreement) was not reported. The objective of this study was to assess whether the agreement between the QMS assay and an LC-MS/MS method was clinically acceptable for use interchangeably in therapeutic everolimus monitoring.Whole blood samples from organ-transplanted patients on everolimus therapy were analyzed by both QMS (on Architect ci4100 analyzer) and LC-MS/MS. Paired results were compared using paired Student t test, Bland-Altman plots, and Deming regression analysis. The proportions of falsely supratherapeutic and subtherapeutic results on the QMS assay compared with the LC-MS/MS were calculated.Among 250 samples (169 patients), mean everolimus concentrations determined by LC-MS/MS and QMS assays were 4.8 ± 2.1 ng/mL and 6.3 ± 2.1 ng/mL, respectively (P0.001), with 95% lines of agreement between -2.1 and 5.2 ng/mL, a range corresponding to 152% of the mean concentration. When stratified by the type of transplant, a similar positive bias was found in each subgroup (all P0.014). Sixty-nine percent of the samples yielding supratherapeutic concentrations (8 ng/mL) on the QMS assay were within the therapeutic range on the LC-MS/MS.The everolimus QMS immunoassay, using the Architect ci4100 analyzer, had a significant positive bias compared with LC-MS/MS, with a wide range between the limits of agreement. The lack of agreement may result in inadequate everolimus dose adjustments, suggesting that the QMS assay cannot be used interchangeably with the LC-MS/MS method for therapeutic everolimus monitoring in organ-transplanted patients.

To characterize poison exposures in young Israeli military personnel as reported to the national poison center.Retrospective poison center chart review over a 14-year period. Cases included were Israeli soldiers aged 18-21 years, the compulsory military service age required by the Israeli law.1770 records of poison exposures in young military personnel were identified. Most exposed individuals involved males (n = 1268, 71.6%). Main routes of exposure were ingestion (n = 854, 48.3%), inhalation (n = 328, 18.6%) and ocular (n = 211, 11.9%). Accidents or misuse (n = 712, 40.2%) were the most frequently reported circumstances, followed by suicide attempts (370, 20.9%), and bites and stings (161, 9.1%). More than half of the cases involved chemicals (n = 939, 53.1%); hydrocarbons, gases and corrosives were the main causative agents. Pharmaceuticals (mainly analgesics) were involved in 519 (29.3%) cases, venomous animals (mainly scorpions, centipedes, and snakes) in 79 (4.5%). Clinical manifestations were reported in 666 (37.6%) cases, mostly gastrointestinal, neurologic, and respiratory. The vast majority of cases (1634, 92.3%) were asymptomatic or mildly affected; no fatalities were recorded. In 831 (46.9%) cases the clinical toxicologist recommended referral to an emergency department; ambulatory observation was recommended in 563 (31.8%) cases, and hospitalization in 86 (4.9%).Our data show that poison exposures among young soldiers involve mainly males, accidents, misuse and suicides, oral route and chemicals; most exposures were asymptomatic or with mild severity. Repeated evaluations of poison center data pertaining to military personnel is advised for identifying trends in poison exposure and characteristics in this particular population.

Calcium channel blocker (CCB) overdose is a potentially fatal poisoning. The use of intravenous lipid emulsion (ILE) therapy for CCB poisoning has emerged in the past few years. In 2017, the American College of Medical Toxicology published interim guidance for the use of ILE resuscitation in these cases. We report an uncommon complication of ILE, acute respiratory distress syndrome, treated with veno-venous extracorporeal membrane oxygenation (ECMO). Case report: A 40-year-old hypertensive woman presented with shock (blood pressure 62/34 mmHg, pulse 86/ min) following ingestion of 4,800 mg verapamil slow release and 1,500 mcg clonidine during a suicide attempt. She was treated with calcium gluconate, sodium bicarbonate, IV high dose insulin, IV glucagon, cardiac amines and vasopressors without response (blood pressure 69/37 mmHg, pulse 78/min). ILE was initiated, and two hours later, she developed acute respiratory failure necessitating intubation and mechanical ventilation. Due to poor oxygenation (pO2 44 mmHg; FiO2 100%) emergent veno-venous ECMO was instituted. After one hour her blood pressure increased to 104/50 mmHg (pulse 80, pO2 75 mmHg), and continued so until weaning from ECMO and ventilation. Conclusion: Acute respiratory distress syndrome can be a major life threating complication following ILE; venovenous ECMO is suggested for its treatment.

Exposure to silica gel, a common desiccant, is considered common and non-toxic although data are limited.To evaluate the characteristics of silica gel ingestion, and to attempt to estimate the associated health care costs.We conducted a one year retrospective review of charts of a national poison information center to characterize ingestions of silica gel and estimate its direct cost to health care services. Cost evaluation was based on emergency department and community clinic tariffs (NIS 807/US$ 213 and NIS 253/US$ 67, respectively).A total of 546 cases were recorded, 2.1% of the annual calls to the poison information center. Most ingestions occurred in children younger than 6 years old (91.4%, 65.2%2 years). Median monthly exposure was 42; the peak (74) occurred in April, before the Passover holiday. Sixty calls (11%) came from health care facilities and the rest were reported by the public; 2.7% were symptomatic, mainly mild self-limited mouth and throat discomfort. The direct annual treatment cost of patients who referred themselves to health care facilities without consulting first with the Poison Center (n = 60) was NIS 24,598/US$ 6507 (emergency department and community clinic visit fees).Silica gel ingestion is relatively common, occurring mainly in young children; it is rarely symptomatic but is a source of unnecessary referrals to health care facilities. The potential annual saving by preventing unnecessary referrals due to poison information center advice was estimated at NIS 375,678/US$ 99,383. The availability of poison information center services may prevent unnecessary referrals to health care facilities and thus save costs.

The Israel National Poison Information Center (IPIC), Rambam Health Care Campus, provides 24 hour telephone consultations in clinical toxicology as well as drug and teratogen information. It participates in research, teaching and regulatory activities, and also provides laboratory services.To report data on the epidemiology of poisonings and poison exposures in Israel.We made computerized queries and descriptive analyses of the medical records database of the IPIC during 2012.A total of 31,519 poison exposure cases were recorded, a 157.6% increase compared with 1995. Children6 years of age were involved in 43.1% of cases; 74.0% of calls were made by the public and 23.7% by physicians; 74.8% of exposures were unintentional and 9.1% intentional. Chemicals were involved in 35.8% of all cases (single and multiple substances), pharmaceuticals in 48.8%, bites and stings in 3.8%, and plants and mushrooms in 1.6%. Substances most frequently involved were analgesics, cleaning products and antimicrobials. Clinical severity was moderate/major in 3.4%. Substances most frequently involved in moderate/major exposures were corrosives, insecticides and snake venom. Four fatalities were recorded; all were intentional exposures in adults (corrosive, medications, energy drink).Poison exposures and poisonings have increased significantly and have contributed substantially to morbidity and mortality in Israel. The IPIC database is a valuable national resource for the collection and monitoring of poisoning exposure cases. It can be used as a real-time surveillance system for the benefit of public health. It is recommended that reporting to the IPIC become mandatory and its activities be adequately supported by national resources.

Xylene is a commonly used toxic volatile organic solvent. Diagnosis of acute xylene poisoning is limited by the lack of a readily available analytic assay. Methylhippuric acid, a metabolite of xylene excreted in the urine, is used for biomonitoring occupational exposures to xylene. We report two cases of acute occupational poisoning from xylene inhalation suggested by determination of high urinary methylhippuric acid. Two 21 and 23 years old healthy male adults collapsed after inhaling an unknown paint thinner during painting. On admission to the emergency department, they were confused and agitated, without hemodynamic or respiratory impairment. Admission urinary methylhippuric acid determined by HPLC with UV detector were 2.57 and 2.68 g/g creatinine (Biologic Exposure Index, BEI, 1.5 g/g creatinine). Urinary hippuric acid was below the previously used BEI for toluene. Mild increases in alanine aminotransferase (80 U/L) and aspartate aminotransferase (71 U/L) were found 12 hours after exposure, returning to normal after 24 hours. The patients gradually regained full consciousness within 24 hours and discharged after 48 hours' observation without any sequelae. High urinary methylhippuric acid concentrations suggested the diagnosis of acute xylene poisoning following its inhalation. Diagnosis in previous reports of acute xylene poisonings relied on history and clinical manifestations. Urinary methylhippuric acid assay is specific and available in special laboratories. It is suggested to determine urinary methylhippuric acid together with metabolites of other widely available organic solvents (e.g., hippuric acid, trichloroacetic acid) whenever unintentional exposure or abuse of volatile organic compounds is suspected.