Severe outcomes following pediatric cannabis intoxication: a prospective cohort study of an international toxicology surveillance registry.

INTRODUCTION: An increasing number of jurisdictions have legalized recreational cannabis for adult use. The subsequent availability and marketing of recreational cannabis has led to a parallel increase in rates and severity of pediatric cannabis intoxications. We explored predictors of severe outcomes in pediatric patients who presented to the emergency department with cannabis intoxication. METHODS: In this prospective cohort study, we collected data on all pediatric patients (<18 years) who presented with cannabis intoxication from August 2017 through June 2020 to participating sites in the Toxicology Investigators Consortium. In cases that involved polysubstance exposure, patients were included if cannabis was a significant contributing agent. The primary outcome was a composite severe outcome endpoint, defined as an intensive care unit admission or in-hospital death. Covariates included relevant sociodemographic and exposure characteristics. RESULTS: One hundred and thirty-eight pediatric patients (54% males, median age 14.0 years, interquartile range 3.7-16.0) presented to a participating emergency department with cannabis intoxication. Fifty-two patients (38%) were admitted to an intensive care unit, including one patient who died. In the multivariable logistic regression analysis, polysubstance ingestion (adjusted odds ratio = 16.3; 95% confidence interval: 4.6-58.3; P < 0.001)) and cannabis edibles ingestion (adjusted odds ratio = 5.5; 95% confidence interval: 1.9-15.9; P = 0.001) were strong independent predictors of severe outcome. In an age-stratified regression analysis, in children older than >10 years, only polysubstance abuse remained an independent predictor for the severe outcome (adjusted odds ratio 37.1; 95% confidence interval: 6.2-221.2; P < 0.001). As all children 10 years and younger ingested edibles, a dedicated multivariable analysis could not be performed (unadjusted odds ratio 3.3; 95% confidence interval: 1.6-6.7). CONCLUSIONS: Severe outcomes occurred for different reasons and were largely associated with the patient's age. Young children, all of whom were exposed to edibles, were at higher risk of severe outcomes. Teenagers with severe outcomes were frequently involved in polysubstance exposure, while psychosocial factors may have played a role.

The epidemiology of wild mushroom poisoning in Israel.

Wild mushroom (macrofungi) picking has become a popular activity in Israel in recent years. Besides the estimated 135 edible species, the mycobiota of Israel includes also around 65 poisonous and potentially dangerous species. We conducted a long-term retrospective study to monitor the frequency, severity, seasonal character, species composition, and geographic distribution of mushroom exposure and poisoning in Israel. Using data collected by the Israel Poison Information Center in Rambam Health Care Campus, Haifa, during the years 2010-2021, we report that only 4% of cases of exposures due to biological agents were caused by mushrooms. Males were significantly (P < 0.004) more affected than females. Most cases involved either above 18 years of age (41%) or below the age of 6 years (39%). Most of the children under 6 years of age did not develop signs or symptoms of toxicity. During 2017-2021, 128 cases (82.5%) involved the consumption of raw mushrooms, mostly by children under 6 years of age. The most common season of mushroom exposure was rainy winters (P < 0.05). Mushrooms collected from irrigated lawns in the summer also posed a risk. Ingestion of Chlorophyllum molybdites was the leading mushroom ingestion in summer and that of Inocybe species in winter. Our study contributes to improved awareness of mushroom exposure and poisoning patterns among the Israeli population.

Adherence of caregivers of children to advice provided by a National Poison Information Center.

INTRODUCTION: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adherence with prescription drugs in pregnant and breastfeeding women consulting with the Israel Poison Information Center Teratology Service.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION AND CONCLUSIONS: 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.

Arum palaestinum poisoning: revenge of the witch.

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.

Cannabis and synthetic cannabinoid exposure reported to the Israel poison information center: Examining differences in exposures to medical and recreational compounds.

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.

The Effect of a 30-Min Water-Pipe Smoking Session on Cognitive Measures and Cardio-Pulmonary Parameters.

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.

Limited Sampling Strategies Supporting Individualized Dose Adjustment of Intravenous Busulfan in Children and Young Adults.

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 <15% was deemed acceptable. RESULTS: Twelve LSSs were acceptable. Sampling at 0, 120, 180, and 240 minutes after the start of the second infusion (LSS15) yielded the best performance, with DAR deviating from the reference by <10% for 95% of cases; the AUCLSS was determined as follows: AUCLSS = 74.7954 × C(0) + 81.8948 × C(120) + 38.1771 × C(180) + 138.1404 × C(240) + 54.1837. This LSS and LSS13 performed similarly well in an independent external validation. CONCLUSIONS: MLR-based estimates of AUCLSS provide DARs that deviate minimally from the reference. LSSs allow the reduction of patient discomfort, a ∼50% reduction of TDM-related workload for nursing staff and blood loss and a ∼25% reduction in laboratory workload. These benefits may encourage wider use of busulfan TDM, supporting safe and efficacious personalized dosing.

Poisoning in Israel: Annual Report of the Israel Poison Information Center, 2017.

BACKGROUND: 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. OBJECTIVES: To report the epidemiology of poison exposures in Israel. METHODS: We present computerized queries and a descriptive analysis of the medical records database of the IPIC for 2017. RESULTS: A total of 39,928 poison exposure cases were recorded, reflecting increases of 226.3% and 26.7% compared with 1995 and 2012, respectively. Children < 6 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). CONCLUSIONS: 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.

[DIEFFENBACHIA POISONING].

INTRODUCTION: 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.

The clinical effects of the venomous Lessepsian migrant fish Plotosus lineatus (Thunberg, 1787) in the Southeastern Mediterranean Sea.

CONTEXT: 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. OBJECTIVE: To characterize the injuries caused by Plotosus lineatus in the Southeastern Mediterranean Sea. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Poison exposures in young Israeli military personnel: a National Poison Center Data analysis.

CONTEXT: To characterize poison exposures in young Israeli military personnel as reported to the national poison center. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Exploring an herbal "wonder cure" for cancer: a multidisciplinary approach.

CONTEXT AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Silica Gel: Non-Toxic Ingestion with Epidemiologic and Economic Implications.

BACKGROUND: Exposure to silica gel, a common desiccant, is considered common and non-toxic although data are limited. OBJECTIVES: To evaluate the characteristics of silica gel ingestion, and to attempt to estimate the associated health care costs. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Comparison of everolimus QMS immunoassay on Architect ci4100 and liquid chromatography/mass spectrometry: lack of agreement in organ-transplanted patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (P < 0.001), 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 P < 0.014). 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. CONCLUSIONS: 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.

Medication errors outside healthcare facilities: a national poison centre perspective.

Medication errors (ME) are a major concern to healthcare systems. Most studies evaluated ME occurring in healthcare facilities; only few focused on ME outside them. The objective was to characterise ME occurring outside healthcare facilities. A prospective observational follow-up study evaluating all ME occurring outside healthcare facilities reported to a national poison information centre during a 5-month period. For each ME case, a detailed questionnaire was filled and a follow-up call was made within 7 days. The collected data included demographics, circumstances, type of error and outcome. Of 1381 consecutive ME cases were included; 97.8% involved a single incident and 88.3% one drug. The main characteristics of the ME were as follows: children younger than 6 years old (58.9%), parents responsible for 55.6% of cases, wrong dose 34.5% and different medication 30.1%. Analgesics (27.4%) and antimicrobials (12.2%) were the most common pharmaceuticals. The main reasons for the ME were look-alike packaging (31.4%) and misunderstood instructions (28%). Most followed up patients (97.1%) were asymptomatic or mildly affected; there was one severe case and no mortality. Most ME occurring outside healthcare facilities are single incidents, involving young children who were administered a wrong dose or medication due to look-alike packaging or misunderstood instructions with asymptomatic or mild outcome. Improved packaging, labelling and patient education are suggested to reduce ME.

Laboratory and clinical acute effects of active and passive indoor group water-pipe (narghile) smoking.

BACKGROUND: Indoor group water-pipe tobacco smoking, commonly referred to as water-pipe smoking (WPS), especially in coffee shops, has gained worldwide popularity. We performed a comprehensive laboratory and clinical evaluation of the acute effects of active and passive indoor group WPS. METHODS: This comparative study evaluated pre- and post-30-min active and passive indoor group WPS. The outcome parameters were carboxyhemoglobin (COHb), nicotine, and cotinine levels; CBC count; and cardiorespiratory parameters. Exhaled breath condensate (EBC) cytokines and endothelial function (using the EndoPat device [Itamar Medical Ltd]) were measured only in active smokers. Statistical methods used were Student t test, Wilcoxon signed rank test, Fisher exact test, analysis of variance, and Newman-Keuls post hoc test where relevant. RESULTS: Sixty-two volunteers aged 24.9±6.2 years were included; 47 were active smokers, and 15 were passive smokers. COHb level increased postactive WPS (active smokers, 2.0%±2.9% vs 17.6%±8.8%; P<.00001); six subjects (12.7%) had a >25% increase, and two subjects (4.2%) had a >40% increase. Plasma nicotine level increased postactive WPS (active smokers, 1.2±4.3 ng/mL vs 18.8±13.9 ng/mL; P<.0001); plasma cotinine and urinary nicotine and cotinine levels also increased significantly. EBC IL-4, IL-5, IL-10, IL-17, and γ-interferon decreased significantly with postactive smoking; endothelial function did not change. WPS was associated with adverse cardiorespiratory changes. In passive smokers, COHb level increased (0.8%±0.25% vs 1.2%±0.8%, respectively, P=.003) as did respiratory rate. CONCLUSIONS: One session of active indoor group WPS resulted in significant increases in COHb and serum nicotine levels (eightfold and 18-fold, respectively) and was associated with adverse cardiorespiratory health effects. The minor effects found in passive smokers suggest that they too may be affected adversely by exposure to WPS. The results call for action to limit the continuing global spread of WPS in coffee shops. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT1237548; URL: www.clinicaltrials.gov.