[ETHICAL PERSPECTIVES AND DILEMMAS IN PRESCRIBING AND DISPENSING MEDICINAL PRODUCTS IN ISRAEL].

INTRODUCTION: Drug therapy is a central pillar in the provision of medical care. A significant number of doctor-patient encounters conclude with a prescription for a drug. These are subsequently followed by a pharmacist-patient interaction that ends with the dispensing of prescription drugs and/or a recommendation for an over-the-counter drug and other products. In Israel, the fields of medicine and pharmacy are highly regulated with extensive legislation.

Implementation of a Short-term Treatment Protocol in Anemic Patients before Cardiac Surgery.

BACKGROUND: We assessed whether implementation of an immediate preoperative treatment in anemic patients could result in fewer perioperative packed red blood cell (PRBC) transfusions and improved outcomes in a real-world setting. METHODS: From January 1, 2020, to November 31, 2022, we implemented a perioperative protocol for anemic patients (hemoglobin (Hb) level in women <11.5 g/dL, men <12.5 g/dL), which included subcutaneous erythropoietin α, intravenous Iron, and intramuscular vitamin B12 (all given preoperatively) and per os iron and folic acid given once a day postoperatively. We retrospectively compared all patients receiving the protocol to all eligible patients who were operated upon in the 4 years prior to implementation of the protocol. Primary outcome was amount of PRBC transfusions during surgery and index admission. RESULTS: In the months after protocol implementation, 114 patients who received the treatment protocol were compared with 236 anemic patients in the 4 years prior to who did not receive the protocol. The treatment reduced total PRBC use (control group median 4 [2-7] units vs. treatment 2 [1-3] units, p < 0.0001) and the incidence of postoperative blood products transfusions (treatment group 58 patients, 50.88% vs. control group 177 patients, 75%, p < 0.0001). Hb prior to discharge was higher among the protocol group (treatment median 9 g/dL [8.3-9.5 g/dL] vs. control 8.6 g/dL [8.1-9.1 g/dL], p = 0.0081). CONCLUSION: Despite some differences compared with previously described protocols, the implementation of a perioperative treatment protocol for anemic patients was associated with a reduction in PRBC transfusion in a real-world setting.

An outbreak of severe coagulopathy in northern Israel among users of illicit synthetic cannabinoids adulterated with brodifacoum.

INTRODUCTION: Adulteration of illicit drugs is a well-known phenomenon that may expose consumers to unexpected adverse effects. We report a large outbreak of severe coagulopathy in northern Israel during nine months in 2021-2022 among users of synthetic cannabinoids adulterated with a long-acting anticoagulant, brodifacoum. METHODS: We performed a retrospective cohort study based on data extracted from the Israeli National Poison Information Center database and from electronic medical patient records at three participating hospitals. Confiscated drug samples and blood samples obtained at admission in a subgroup of patients were tested for the presence of long-acting anticoagulants. RESULTS: We identified 98 patients affected by the outbreak. All patients had a prolonged international normalized ratio on admission, and in 69%, the blood was non-coagulating. For patients treated in the three participating centers (n = 72), the presenting complaint was overt bleeding in 79% of patients, most commonly in the urinary (53%) and gastrointestinal tracts (50%). The most severe complications were intracranial bleeding (4%), hemothorax (3%), pericardial bleeding (1%), and four patients died. Brodifacoum was detected in all available blood samples (median concentration 207 µg/L, interquartile range 112-349 µg/L, range 45-1,118 µg/L), and the drug samples contained both brodifacoum and the synthetic cannabinoid ADB-BUTINACA. All patients were treated with high-dose phytomenadione (vitamin K1) and additionally by packed red blood cell transfusions, fresh frozen plasma, and/or 4-factor prothrombin complex concentrate when indicated. The most frequent phytomenadione (vitamin K1) dose regimen was initially 20 mg intravenously every eight hours, and at discharge, 20 mg orally three times daily. CONCLUSIONS: Outbreaks of severe coagulopathies in users of synthetic cannabinoids adulterated with a long-acting anticoagulant continue to erupt in different regions of the world. Rapid recognition of an outbreak requires a high index of suspicion when confronting young, otherwise healthy subjects with otherwise unexplained severe coagulopathy.

Safety Signal Evaluation of a Risk of Syncope and Dizziness Not Related to Bleeding or Stroke in Direct Oral Anticoagulant-treated Patients.

PURPOSE: In clinical studies, rivaroxaban treatment has been associated with increased incidence of syncope not related to bleeding, anemia, or stroke. The study objective was to evaluate the occurrence of dizziness and/or syncope not related to bleeding, anemia, or stroke in patients treated with direct oral anticoagulants (DOACs). METHODS: A retrospective, observational, comparative study of adult patients diagnosed with atrial fibrillation and treated with DOACs was conducted using digital retrieval of medical records. Primary outcomes were an emergency department (ED) visit or hospitalization due to syncope, fall, or dizziness. Cases related to bleeding, anemia, or stroke were excluded. Separate examination of a sample of records validated the data. FINDINGS: Of 6467 eligible patients, 256 (4%) were hospitalized or referred to the ED due to fall, syncope, or dizziness during a mean observation period of 20.1 months. After multivariate regression analysis, statistically independent risk factors were found to be age (hazard ratio [HR] = 1.04, P < 0.0001) and benzodiazepine use (HR = 1.33, P = 0.03). No statistically significant difference was found among the different DOAC types regarding the primary outcome (apixaban and rivaroxaban HR = 0.97, P = 0.85; dabigatran and rivaroxaban HR = 1.2, P = 0.386). IMPLICATIONS: The study results failed to confirm the claimed association between the use of a DOAC and syncopal symptoms unrelated to bleeding, anemia, or stroke in this relatively large Israeli patient population. Age and benzodiazepine treatment were significant independent risk factors of these events.

Carbamazepine Therapy After Bariatric Surgery: Eight Sleeve Gastrectomy Cases and Review of the Literature.

Bariatric surgery modifies the anatomy and physiology of the gastrointestinal tract. Carbamazepine (CBZ) is an anticonvulsant with multiple neuropsychiatric indications. Given CBZ physicochemical properties and narrow therapeutic index, bariatric surgery may potentially introduce clinically significant changes in CBZ oral absorption and bioavailability. In this communication, we describe eight patients undergoing sleeve gastrectomy (SG) and treated with CBZ, including therapeutic drug monitoring (TDM) and dosage adjustments at different timeframes before vs. after the surgery (< 3, 4-6, and 7-12 months post-SG), as well as clinical outcomes. We then provide a review of the available literature on CBZ therapy among bariatric patients, concluding with a mechanistic analysis of the results. Four of the eight patients presented with decreased post-SG CBZ levels, and two of them also experienced significant worsening of their previously well-controlled disease. Overall, altered CBZ levels are likely for at least a year after SG. Clinical recommendations include consultation with a clinical pharmacist, careful clinical monitoring, and periodic TDM after (vs. before) the bariatric surgery.

Can isosorbide dinitrate oral spray serve as an immediate bridging therapy for a mass cyanide poisoning?

OBJECTIVE: In this proof-of-concept study, the aim was to evaluate the short-term clinical effectiveness of isosorbide dinitrate (ISDN) oral spray in non-anaesthetized cyanide-poisoned swine. METHODS: A comparative study was conducted using domestic swine. Animals were intravenously poisoned with potassium cyanide (KCN), either 2 mg/kg or 4 mg/kg dose. Two control groups (one for each cyanide dose) were not further treated. Two other groups (one for each cyanide dose) were treated within 1 min after poisoning with ISDN oral spray: 3 spray actuations (averaging a total of 3.75 mg) after the lower cyanide dose and 4 spray actuations (averaging a total of 5.0 mg) after the higher dose. The study outcomes were clinical score, time to death, and blood tests including pH, lactate, and methemoglobin levels. RESULTS: All the animals started to convulse within 20 to 30 sec after KCN poisoning, then became unresponsive and hemodynamically depressed after another 20 to 30 sec. After the KCN 2 mg/kg dose, 3 of 4 control animals survived, while all treated animals survived. Compared with control animals, ISDN-treated animals displayed significantly better clinical scores starting 5 min after KCN poisoning. Acidosis was significantly more pronounced in the untreated animals. After the KCN 4 mg/kg dose, similar survival rates were observed for control and ISDN-treated groups (1/4), but treated animals had longer time to death and better pH and lactate levels. CONCLUSION: ISDN oral spray administration following KCN poisoning in this porcine model did not result in statistically significant increased survival. However, based on clinical scores and clinical laboratory values, ISDN may benefit as a bridging countermeasure until currently-available specific cyanide antidotes can be administered. Further research is warranted to better characterize this potential role of ISDN in cyanide poisoning.

Adherence to Monitoring Guidelines of Amiodarone Adverse Reactions.

BACKGROUND: Amiodarone treatment frequently causes adverse reactions. Clinical guidelines warrant a comprehensive assessment prior to chronic treatment with amiodarone and repeated monitoring for the appearance of adverse reactions. OBJECTIVE: To evaluate adherence to these guidelines. METHODS: A retrospective chart review of electronic medical records of adult patients treated with oral amiodarone for at least 12 months. RESULTS: One hundred patient records were analyzed; 97% of patients were evaluated for thyroid and liver functions prior to treatment. Liver functions were properly monitored every 6 months in 96% of patients and thyroid function in only 59%. Most (84%) patients completed a chest X-ray before treatment; only 2% completed a respiratory function test. None have performed a chest X-ray annually. Sixty-four percent of the patients were examined by an ophthalmologist prior to treatment; periodic ophthalmic surveillance was not consistent. Neurological and dermatological evaluations were not recorded for any of the patients, unless symptoms appeared. Only 50% were adherent to annual cardiac reassessment. CONCLUSIONS: Adherence to recommended clinical guidelines for monitoring amiodarone adverse reactions is poor. Interventions to improve compliance with these guidelines are needed.

Safety of brotizolam in hospitalized patients.

PURPOSE: The objective of this study was to evaluate the safety of brotizolam in hospitalized patients. METHODS: A single-center, comparative retrospective cohort analysis of patients hospitalized in internal medicine wards. Patients treated with brotizolam were compared to patients not treated with any benzodiazepines during hospitalization. Primary outcome was any of the following safety events: mechanical ventilation, delirium, and falls. RESULTS: Six hundred patients were included after exclusion in the final analysis; 300 treated with brotizolam (treatment) and 300 not treated with any benzodiazepines (comparator). The brotizolam-treated patients were older with more comorbidities and psychotropic medications. After adjustment using multivariate logistic regression analysis with propensity score, the primary outcomes occurred at significantly higher rates in treated patients than in untreated patients (17 vs. 2 events; OR = 7.33). Any psychotropic medication administered during hospitalization was found by logistic regression to be the main independent risk factor for the studied safety outcomes while age, comorbidities, and the cause of hospitalization were not. CONCLUSIONS: Treatment with brotizolam during hospitalization in internal medicine wards is linked to a higher risk of respiratory deterioration, delirium, and falls. Use of psychotropic medications during hospitalization is the main independent risk factor of safety outcomes. Further research is needed to fully evaluate the risks and benefits of sleep induction medications in hospitals.

Effectiveness of isosorbide dinitrate in cyanide poisoning as a function of the administration timing.

BACKGROUND: Better and safer antidotes against cyanide poisoning are needed. Prior study has shown a favorable effect of isosorbide dinitrate (ISDN) on the survival of cyanide-poisoned rabbits when administered as early as 1 min after poisoning. The aim of the current study was to further evaluate the efficacy of intravenous ISDN administered in clinically relevant timing for first responders. METHODS: A comparative animal study using 24 rabbits in 4 randomized study groups was performed. Animals were poisoned with intravenous potassium cyanide (1 mg/kg). Animals in Group 1 served as controls and received no treatment. Groups 2-4 animals were treated intravenously with ISDN (50 µg/kg) after poisoning; one group after 3 min, another group after 5 min and the last after 7 min. Animals were observed for 30 min after poisoning. The study endpoints included survival rate, clinical status, blood pressure, pulse per minute, blood lactate and pH. RESULTS: Five of 6 animals (83.3%) from every treatment group survived the whole observation period while all control untreated animals died. All the rabbits collapsed immediately after exposure, showing rapidly deteriorated vital signs with lactic metabolic acidosis (peak blood lactate levels of 18.1 to 19.0 mmol/L on average at 10 min post exposure). Vital signs, clinical scores, and blood gases of treated rabbits gradually improved. CONCLUSION: Poisoned rabbits showed improved short-term survival following the administration of ISDN up to 7 min after lethal cyanide poisoning of. We see a potential for ISDN as an antidote against cyanide poisoning.

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.

[LONG TERM TREATMENT WITH MACROLIDES IN CHRONIC LUNG DISEASES].

INTRODUCTION: Macrolide agents have both antibacterial properties as well as various effects on the inflammatory system. In recent years there is growing evidence regarding the favourable effects of macrolides in a range of chronic respiratory conditions. Historically, erythromycin and clarithromycin were found to stabilize pulmonary deterioration in diffuse panbronchiolitis. In cystic fibrosis patients colonized with pseudomonas aeruginosa, long term treatment with azithromycin reduces exacerbations and presents improved lung function. A similar effect on prevention of exacerbations has been demonstrated in noncystic fibrosis bronchiectasis. In patients undergoing lung transplantation, long term azithromycin prevents bronchiolitis obliterans syndrome. In patients with chronic obstructive pulmonary disease (COPD), azithromycin prevents acute exacerbations. Chronic treatment with macrolides is associated with adverse effects including gastrointestinal symptoms, interactions with other drugs and cardiovascular complications. Of the macrolides, azithromycin is associated with the lowest interactions and adverse effects and is also the most investigated.

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.

Is rivastigmine safe as pretreatment against nerve agents poisoning? A pharmacological, physiological and cognitive assessment in healthy young adult volunteers.

Rivastigmine, a reversible cholinesterase inhibitor, approved as a remedy in Alzheimer's disease, was suggested as pretreatment against nerve agents poisoning. We evaluated the pharmacokinetic, pharmacodynamic, physiologic, cognitive and emotional effects of repeated rivastigmine in young healthy male adults, in a double blind, placebo controlled crossover trial. Three groups completed 3 treatment periods: 0, 1.5 and 3mg twice a day, for a total of 5 intakes. Parameters monitored were: vital signs, ECG, laboratory tests, sialometry, visual accommodation, inspiratory peak flow, and cognitive function tests. Adverse reactions were mild. Peak blood levels and peak cholinesterase inhibition increased with repeated intakes, and high variability and non-linear pharmacokinetics were demonstrated. In addition, two cognitive functions were affected (perceptual speed and dynamic tracking). The complicated pharmacological profile and the high inter-personal variability limit the potential use of rivastigmine as pretreatment for war fighters and first responders.

Early administration of isosorbide dinitrate improves survival of cyanide-poisoned rabbits.

CONTEXT: More effective, rapidly delivered, safer antidotes are needed for cyanide poisoning. Previous study has demonstrated a beneficial effect of isosorbide dinitrate on the survival of cyanide-poisoned mice. OBJECTIVE: To evaluate the effectiveness of isosorbide dinitrate compared with that of sodium nitrite in cyanide poisoning. MATERIALS AND METHODS: A comparative animal study was performed using 18 rabbits, randomized into 3 study groups. Animals were poisoned intravenously with potassium cyanide (1 mg/kg). The first group was not given any further treatment. The second and third groups were treated intravenously 1 min after poisoning with sodium nitrite (6 mg/kg) and isosorbide dinitrate (50 µg/kg), respectively. The primary outcome was short-term survival of up to 30 min. Secondary outcomes included time to death, a clinical score, mean blood pressure, pulse, blood pH, and lactate and methemoglobin levels. RESULTS: Rabbits treated with isosorbide dinitrate or sodium nitrite survived while only one untreated rabbit survived. Median time to death of the 5 poisoned and untreated animals was 10 min. All the animals collapsed soon after poisoning, exhibiting rapidly disturbed vital signs and developed lactic metabolic acidosis; average peak blood lactate levels were 15.5-19.1 mmol/L at 10 min after poisoning. The treated animals improved gradually with practically full recovery of the clinical scores, vital signs, and blood gas levels. Sodium nitrite administration raised methemoglobin to an average peak of 7.9%, while isosorbide dinitrate did not change methemoglobin levels. CONCLUSION: Early administration of isosorbide dinitrate improved the short-term survival of cyanide-poisoned rabbits. Isosorbide dinitrate shows potential as an antidote for cyanide poisoning and may exert its effect using a nitric-oxide-dependent mechanism.

Airway control in case of a mass toxicological event: superiority of second-generation supraglottic airway devices.

INTRODUCTION: Early respiratory support and airway (AW) control with endotracheal intubation (ETI) are crucial in mass toxicology events and must be performed while wearing chemical personal protective equipment (C-PPE). AIM: The aim of this study is to evaluate the efficiency of AW control by using second-generation supraglottic AW devices (SADs) as compared with ETI and first-generation SAD while wearing C-PPE. METHODS: This is a randomized crossover trial involving 117 medical practitioners. Four AW management devices were examined: endotracheal tube, the first-generation SAD, laryngeal mask AW unique and 2 second-generation SAD, the laryngeal tube suction disposable, and supreme laryngeal mask AW (SLMA). Primary end point measured were success or failure, number of attempts, and time needed to achieve successful device insertion. Secondary end point was a subjective appraisal of the AW devices by study population. RESULTS: More attempts were required to achieve AW control with endotracheal tube, with and without C-PPE (P<.001). Time to achieve AW control with ETI was, on average, 88% longer than required with other devices and improved with practice. The mean times to achieve an AW were longer when operators were equipped with C-PPE as compared with standard clothing. Subjectively, difficulty levels were significantly higher for ETI than for all other devices (P<.0001). CONCLUSIONS: When compared with ETI, the use of SADs significantly shortened the time for AW control while wearing C-PPE. Second-generation SAD were superior to laryngeal mask AW unique. These finding suggest that SADs may be used in a mass toxicology event as a bridge, until definite AW control is achieved.

Prevention of organophosphate-induced chronic epilepsy by early benzodiazepine treatment.

Poisoning with organophosphates (OPs) may induce status epilepticus (SE), leading to severe brain damage. Our objectives were to investigate whether OP-induced SE leads to the emergence of spontaneous recurrent seizures (SRSs), the hallmark of chronic epilepsy, and if so, to assess the efficacy of benzodiazepine therapy following SE onset in preventing the epileptogenesis. We also explored early changes in hippocampal pyramidal cells excitability in this model. Adult rats were poisoned with the paraoxon (450µg/kg) and immediately treated with atropine (3mg/kg) and obidoxime (20mg/kg) to reduce acute mortality due to peripheral acetylcholinesterase inhibition. Electrical brain activity was assessed for two weeks during weeks 4-6 after poisoning using telemetric electrocorticographic intracranial recordings. All OP-poisoned animals developed SE, which could be suppressed by midazolam. Most (88%) rats which were not treated with midazolam developed SRSs, indicating that they have become chronically epileptic. Application of midazolam 1min following SE onset had a significant antiepileptogenic effect (only 11% of the rats became epileptic; p=0.001 compared to non-midazolam-treated rats). Applying midazolam 30min after SE onset did not significantly prevent chronic epilepsy. The electrophysiological properties of CA1 pyramidal cells, assessed electrophysiologically in hippocampal slices, were not altered by OP-induced SE. Thus we show for the first time that a single episode of OP-induced SE in rats leads to the acquisition of chronic epilepsy, and that this epileptogenic outcome can be largely prevented by immediate, but not delayed, administration of midazolam. Extrapolating these results to humans would suggest that midazolam should be provided together with atropine and an oxime in the immediate pharmacological treatment of OP poisoning.

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.

[Cholinesterase inhibitor poisoning: a complicated medical challenge].

Exposure to insecticides, mainly cholinesterase inhibitors, is a global problem with substantial morbidity and mortality. Risk of intoxication is increased in rural areas where there is high availability and proximity of insecticides to families and children. Neglected storage and inadequate practice lead to dangerous exposure. Strict regulations and appropriate safety measures are needed for the prevention of exposure to insecticides. Broad toxicological knowledge is necessary in order to treat organophosphate and carbamate poisoned patients. Diagnosis is not trivial, since the identity of the poison is not always apparent. Multiple exposures including organic solvents are possible. The clinical presenting can be confusing. Measurement of cholinesterase activity is mandatory in establishing the diagnosis. Prompt treatment with proper antidotes and respiratory support is indicated. Early administration of anticonvulsants may mitigate central neurologic complications. Monitoring neurologic and cardiac function is advised for rapid identification of complications and prognosis evaluation. Meticulous preparedness of health care providers for insecticide poisoning is needed from the pre-hospital phase to emergency departments and the different hospital wards.

Severe paramethoxymethamphetamine (PMMA) and paramethoxyamphetamine (PMA) outbreak in Israel.

CONTEXT: Paramethoxymethamphetamine (PMMA) is a hallucinogenic synthetic substituted amphetamine that was not included in the Israeli Controlled Substance Act (CSA). OBJECTIVE: To report a severe PMMA and paramethoxyamphetamine (PMA) outbreak. PATIENTS AND METHODS: The Israeli national forensic toxicology laboratory analyzes the body fluids of unnatural deaths by means of screening immunoassays and chromatographic confirmation and quantification. Samples are referred to this laboratory by the Israeli Forensic Medicine Institute and by hospitals following consultation with the Israel Poison Information Center. The forensic toxicology laboratory began determining PMMA and PMA in February 2007. In all fatal cases with a positive immunoassay screen for amphetamines, a chromatographic analysis of PMA and PMMA was performed. The laboratory and demographic data of consecutive patients in whom PMMA or PMA were detected, were collected during 1 year and subjected to descriptive analysis. RESULTS: Of 108 fatal cases with a positive screen for amphetamines, 32 were confirmed. Twenty-four of the 32 cases tested positive for PMMA and PMA--age 27 ± 5 years, 79.2% males, post mortem whole blood PMMA and PMA concentrations 0.35 ± 0.24 and 2.72 ± 1.67 mcg/mL, respectively. Co-exposures were detected in 17 (70.8%) fatalities; including methylenedioxymethamphetamine, methylenedioxyamphetamine, cocaine, cannabinoids, cathinone derivatives, ephedrine/pseudoephedrine, opiates, and ethanol. In addition, five non-fatal male cases were identified; age 32 ± 5 years, four had co-exposures to cocaine, cathinone derivatives, and cannabinoids. These findings led to the inclusion of PMMA in the CSA in July 2007, resulting in only three more fatalities in the following year. DISCUSSION: We report an outbreak of PMMA and PMA poisoning resulting in 24 fatalities, and the post mortem whole blood and urine concentrations of these two compounds. PMA was probably the result of PMMA metabolism. Stimulant co-exposures may have contributed to the severity of the poisoning. CONCLUSION: Forensic laboratory and poison center co-operation is important in identifying a new drug of abuse.