As of November 20, 2019:

2290 cases of e-cigarette, or vaping, product use-associated lung injury (EVALI) from 49 states (except Alaska), District of Columbia and 2 U.S. territories.

• Largest number of cases (150-199) reported from CA, TX and IL
• 47 deaths

Analysis of 29 bronchoalveolar lavage (BAL) fluid samples from EVALI patients submitted to CDC from 10 states showed:

• Vitamin E acetate in all samples 
• THC: 82%
• Nicotine: 62%
• No other chemicals of concern were identified (e.g. plant oil, mineral oil, terpenes, etc.) 

*** Vitamin E acetate appears to be associated with EVALI but the investigation is continuing.*** 

• Oral ingestion of vitamin E acetate does not cause harm.
• High dose vitamin E supplementation (>2000 IU/day [2000 mg/day]) can cause GI symptoms: nausea, vomiting, diarrhea and abdominal pain.

Some research has suggested that oral vitamin E use has potential beneficial effects (i.e. anti-inflammatory/antioxidant) in the lung (e.g. asthma and allergic lung disease), cardiovascular disease and prostate cancer (Cook-Mills JM et al. 2013; Jiang Q et al. 2001)

Common uses of vitamin E

• Topical cosmetic skin products (skin cream) for antioxidant effect.
• Essential dietary vitamin (fat soluble) found in many food items and as dietary supplement.
• In vaping products: vitamin E is used as an additive/thickening agent in THC containing e-cigarette, or vaping products.

There is limited to no data on pulmonary effect of vitamin E from inhalation in the scientific literature.

Stay tuned for additional updates from CDC.

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Metformin is one of the most commonly prescribed oral hypoglycemic agents. Metformin associated lactic acidosis (MALA) is uncommon but potentially life-threatening complication of metformin overdose. 

Lactic acidosis occurs due to inhibition of mitochondrial glycerophosphate dehydrogenase, resulting in decreased conversion of lactic acid to pyruvate.

A small retrospective study (using Illinois Poison Center data) attempted to characterize the development of MALA after an acute overdose.

MALA was defined as 

• Lactate: > 5 mmol/L
• Acidemia: (HCO₃< 20 mmol/L or pH < 7.35)

Results

40 cases of MALA identified between Jan. 2001 to Dec. 2014

• Meadian age: 41 year
• Female: 55%
• Acute on chronic ingestion: 62.5%
• Hypoglycemia: 3 (7.5%)

Time to development of MALA (n=30)

• <=6 hours: 18 (60%)
• 6-12 hours: 9 (30%)
• >12 hours: 3 (10%)
• Unknown: 10

Death: 1 (2.5%)

Conclusion

1. The majority of MALA developed within 6 hours. However, delayed onset of MALA can occur, up to 12 hours post ingestion.
2. Minimum of 12 hour of observation is recommended after an acute metformin overdose.

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Droperidol has recently become available again in select U.S. institutions. It has been used as an antiemetic and to treat agitation prior to the FDA’s black box warning (for QT prolongation) and national shortage. 

Recently, a retrospective study was conducted (Melbourne, Australia) in the use of droperidol in the management of cannabinoid hyperemesis syndrome (CHS).

Results

689 medical records were identified from January 2006 to December 2016.

76 cases met diagnostic criteria of CHS (below)

• Long-term cannabis use
• Symptoms of recurrent vomiting
• Absence of illness that could otherwise explain symptoms.

Droperidol group (DG) = 37; no droperidol group (NDG)= 39 

Median length of stay: 

• DG: 6.7 hr vs. NDG: 13.9 hours (p=0.014)

Median time to discharge after final drug administration: 

• DG: 137 min (IQR: 65, 203) vs. NDG: 185 min (IQR: 149, 403)

Frequency of droperidol (dose) used: 

1. 0.625 mg (n=25)
2. 1.25 mg (n=20)
3. 2.5 mg (n=17)

Metoclopramide and Ondansetron use in non-droperidol group was twice that of droperidol group

Conclusion

• Droperidol use to treat CHS associated nausea/vomiting resulted in decreased length of stay and lower use of antiemetics.  

Patients with drug-induced cardiogenic shock [DIC] (e.g. overdose of CCB/BB, membrane stabilizing agents, etc.) are often managed with medical interventions such as vasopressors, bicarbonate infusion, high-dose insulin, lipid emulsion therapy. A fraction of these patients may be refractory to the standard medical therapy. VA-ECMO (venoarterial extracorporeal membrane oxygenation) has been utilized in such situation; yet clinical experience of using VA-ECMO in DIC is limited.

A recent retrospective study of the Extracorporeal Life Support Organization’s ECMO registry showed

• Increasing VA-ECMO utilization for drug-induced cardiogenic shock (n=104) over the past 15 years (2003 to 2018) but it represents a fraction (0.067%) of VA-ECMO use.
• VA-ECMO improved hemodynamic and metabolic status at 24 hrs-post cannulation.
• Persistent acidosis (HCO3 level) and acidemia (pH) at 24 hrs-post cannulation was associated with mortality.
• 52.9% of the cases survived to discharge. 

Conclusion

• VA-ECMO may be clinically beneficial (improvement of hemodynamic and metaboic status) in patients with refractory drug-induce cardiogenic shock

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The rate of suicide attempt has been increasing over the past decade. A recently published article investigated the temporal trend of suicide attempts in adolescent/young adult population (10 – 25 years old) from 2000 to 2018.

 Methods

• All intentional – suspected suicide cases were identified from the National Poison Data System from Jan 1, 2000 to December 31, 2018. 
• Following age groups were compared: 10-12, 13-15, 16-18, 19-21 and 22-25 years old.

Results

• A total of 1,677,435 cases were identified with 0.1% fatality (n=1579).
• Female: 70.6% (n=1,184,691) 
• Single substance (64.1%; n=1,074,423)
• Highest suicide attempt rate: 16-18 years (30.1%; n=504,682)
• Lowest suicide attempt rate: 10-12 years (2.3%; n=38,428)

• The suicide attempt rate increased significantly starting 2011 in 10-12, 13-15 and 16-19 years age groups with seasonal trend
  •  Higher during school months (Sept to May) vs. non-school months (June-August)

Top 5 substance involved in suicide attempt

1. OTC analgesics
2. Antidepressants
3. Sedative hypnotics
4. Antihistamines
5. Antipsychotics

Agents associated with serious medical outcome (after 2011)

1. Antidepressants
2. OTC analgesics
3. Antihistamines 
4. ADHD medications

• ADHD medicaitons: common in 10-15 years population
• Sedative hypnotics (e.g. benzodiazepines): common in older age group (16-25 years)

Conclusion

• Rate of suicide attempt in adolescent and young adults has increase, especially since 2011.
• The substance used in suicide attempt usually involves medications available to the specific age group.
• OTC medications (analgesics and antihistamines) were involved in a third of the suicide attemps.

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E-cigarette (vaping) use has become increasingly popular over the past 10 years, especially among adolescents. Intentional exposure (i.e. ingestion in self harm) of nicotine (e-cigarette liquid) can be life threatening where it can produce mixture of stimulatory (early), cholinergic toxicity and muscle paralysis/respiratory failure by blocking the neuromuscular junction. However, the severity of clinical toxicity in unintentional exposure can vary widely depending on the dose/route/circumstance of their exposure.

A recently published study investigated the characteristics of e-cigarette liquid exposure between Jan 1, 2010 to Dec 31, 2018 using the National Poison Data System

Result

• Total reported exposure: 17,358.
• e-cigarette exposure report increased starting 2013 (n=1435), peaking in 2014 (3742). 2018 (n=2901).

Top 4 clinical/demographic characteristics are listed below.

Age group:

• < 5 years: 64.8%
• 25+ years: 15.4%
• 18-24 years: 8.3%
• 12-17 year: 3.4%

Route of exposure

• Ingestion: 77.5%
• Dermal: 13.0%
• Inhalation/nasal: 10.4%
• Ocular: 7.1% 

Level of care:

• Not referred to health care facility (HCF): 60.9%
• Treated and released from HCF: 27.4%
• Admitted: non-critical care: 0.8%, critical care: 0.6%

Clinical effects - overall

• Vomiting: 25.4%
• Nausea: 11.8%
• Ocular irritation: 11.3%
• Dizziness/vertigo: 5.1%

In <5 years group

• Vomiting: 47.1%
• Cough/choking: 10.2%
• Drowsiness/lethargy: 5.7%
• Nausea: 5.5%

Conclusion

• e-cigarette exposure predominantly occurs in young children (< 5 y/o)
• Clinical toxicity are usually self-limited and often not referred to HCF.
• Severe toxicity is possible, although infrequent, from unintentional exposure.

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Cannabinoid hyperemesis syndrome [CHS] (i.e. cyclic/recurrent nausea, vomiting and abdominal pain) is associated with long-term and frequent use of marijuana. Patients with CHS often report temporary relief of symptoms with hot water/shower exposure. Emergency room providers may encounter a growing number of patients with CHS with increasing legalization of marijuana-containing products.

Topical capsaicin has been gaining interest as a potential adjunct to the conventional management of patients with CHS (e.g. antiemetics, opioids, benzodiazepines and antipsychotics).

A small retrospective study was performed involving 43 patients who had multiple visits, and were treated with and without capsaicin. The primary outcome was the ED length of stay (LOS).

Results

• Most frequently administered medications in both groups were:

1. Anti-emetics
2. Haloperidol
3. Diphenhydramine 

• Median ED LOS: no significant difference
  • Capsaicin vs. non-capsaicin: 179 min (IQR: 147, 270) vs. 201 min (IQR: 168, 310) (p=0.33)

• Capsaicin group showed
  • Decreased opioid used: 69 mg vs. 166.5 mg oral morphine equivalents
  • Fewer additional medication administration: 3 vs. 4 doses (p=0.015)
  • Shorter median time to discharge after last medication administration: 60 min (IQR: 35, 115) vs. 92 min (IQR: 47, 155) (p=NS) 

• 67% of the visit where capsaicin was used required no additional medication.

Conclusion

• Capsaicin use did not decrease ED LOS.
• However, there was a decrease in total medications administered and opioid requirement.

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Breath analyzers are commonly used by law enforcment officers to test for alcohol intoxication. Breath analyzer uses ethanol partition ratio between blood:breath of 1:2100 = 1 gm of ethanol in 2100 mL of breath/air.

Mouth wash products are frequently used for oral hygiene, and at times, to "mask" odor of substances. These products are readily available in any grocery stores or pharmacy and contain upto 26.9% ethanol (e.g. Listerine) (18.9% - Scope; 14.0% - Cepacol).  

Recently, a small study using healthy volunteers (n=11) was published to investigate the impact of limited ethanol exposure (mouth wash and ethanol vapor) on the breath-alcohol concentration (BrAC).

Method

1. Ethanol vapor exposure (856 mg/m3) for 15 minute. 
2. Oral rinse (for 30 sec) using mouth wash containing 22% ethanol, 1 hour after the ethanol vapor exposure
3. Blood and breath samples were collected before, between and after exposure.

Results

Blood: No or very low levels of ethanol (0.002 mg/g) were detected in blood at all collection time for both exposures.

BrAC - first collection -- seconds after exposure

• Ethanol vapor: 0.14 mg/L (0.014 mg/dL)
• Mouth wash: 4.4 mg/L (0.44 mg/dL)

Mean time to negative BrAC level (Swedish statutory limit of 0.1 mg/L = 0.01 mg/dL in air) (FYI: US limit = 80 mg/dL)

• Ethanol vapor: 0.5 min (0.06 - 0.7 min)
• Mouth wash: 11 min (6 - 15 min) 

Conclusion

• Ethanol vapor did not affect the BrAC
• Mouth wash use can transiently increase BrAC; however, their use does not sufficiently increase the BrAC to result in "false positive" based upon US limit.

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Numerous different household products can potentially be misused/abused. One such product is whipped cream charger/propellant that contains nitrous oxide.

Acute toxicity produce dose dependent response

• Euphoria 
• Anxiolysis
• Sedation
• Unconsciousness
• Asphyxiation

Chronic toxicity causes myeloneuropathy (demyelination of the dorsal and lateral columns of the spinal cord) due to vitamin B12 deficiency

• Extremity paresthesias
• Ataxia
• Peripheral sensory neuropathy (loss of vibration sense and proprioception)
• Weakness 
• Hematologic effects: leukopenia, thrombocytopenia, megaloblastic anemia

Management

• Cessation of nitrous oxide use
• Vitamin B12 (cyanocobalamin) repletion (IM)

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Question

A 3 year old is bitten by a spider on his right ear which is causing him intense pain, tachycardia, and muscle cramping. Identify the spider.  What is the treatment?

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Center for Disease Control and Prevention (CDC) recently issued alerts regarding cases of pulmonary illnesses that may be linked to "vaping" (in 15 states with 149 possible cases). These cases are still under investigation but all cases reported vaping weeks/months prior to hospitalization.

Most cases involve young adults who have been using THC-containing products

Common complaints included

• Gradual onset of shortness of breath, cough, and chest pain
• GI symptoms: nausea, vomiting and diarrhea
• Fever, fatigue

Imaging studies:

• Chest x-ray can show bilateral opacity
• CT lung demonstrates ground-glass opacities with sub-pleural sparing.

Clinical course

• Some cases required mechanical intubation
• Corticosteroid treatment appears to improve clinical course
• Infectious evaluation was negative in almost all cases.
• No clear causative etiology has been identified
• No death has been reported 

What to do:

• Inquire about vaping history when treating patients with suspected cases.
• Providers should contact their local health department, poison center or CDC (VapingAssocIllness@cdc.gov) to report possible case of vaping associated pulmonary injury 

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Direct hepatotoxicity from a drug is predictable and dose-dependent.

Most commonly implicated agents include:

• Acetaminophen
• Niacin
• Aspirin
• Cocaine
• IV Amiodarone
• IV methotrexate
• Cancer chemotherapy

On the contrary, idiosyncratic prescription drug-induce liver injury is rare, unpredictable and not related to dose.

Most commonly implicated agents are:

1. Amoxicillin-clavulanate
2. Isoniazid
3. Nitrofurantoin
4. TMP-SMZ
5. Miocycline
6. Cefazolin
7. Azithromycin

Bottom line:

• Drug-induced liver injury is uncommon and can be a diagnostic challenge.
• Recognition of commonly implicated agents can help recognize/identify drug-induced liver injury. 

Hematologic toxicity (coagulopathy/bleeding) can occur with pit viper envenomation. Copperhead is the most commonly implicated pit viper envenomation in the U.S. However, the prevalence of hematologic toxicity from copperhead envenomation is variable, possibly due to regional variation in venom potency and species misidentification. 

An observation study was performing using multi-center (Virginia Commonweath university, University of Virginia Medical Center and Eastern Virginia Medical medical center) electronic hospital/medical records (Jan 1, 2006 to Dec 31, 2016) of suspected copperhead bites. Authors state that copperhead snakes are "nearly exclusively endemic" to the VCU and UVA medical center region.

Results:

388 patients were identified but 244 met inclusion/exclusion criteria.

• Mean age: 34 years
• Male: 59%
• Antivenom administration: 76%
• No bleeding was reported.

Hematologic toxicity: 14%

• Elevated PT: 10.0%
• Elevated PTT: 3.9%
• Thrombocytopenia: 1.2%
• Hypofibrinogenemia: 0.7%

Conclusion

In a small sample of copperhead envenomation in Virginia, “subtle” hematologic abnormalities were observed but clinically significant hematologic toxicity was not observed (i.e. bleeding)

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Pulmonary complications - aspiration, pulmonary edema, etc. are frequently reported in both heroin intoxication and in reversal of opioid overdose with naloxone. 

Suspected opioid overdose victims (N=1831) who received naloxone from EMS providers were studied retrospectively. Pulmonary complications were defined as pulmonary edema, aspiration pneumonia and aspiration pneumonitis.

Results

• Out of hospital naloxone dose > 4.4 mg – 62% more likely of experiencing pulmonary complication (OR 2.14, 95% CI: 1.44 to 3.18) 
• Increased risk of pulmonary complication if initial naloxone dose is > 0.4 mg (OR 2.57, 95% CI 1.45 to 4.54)

Conclusion

Higher out of hospital naloxone administration is associated with increased odds of developing pulmonary complications

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“Push dose pressors” – administration of small doses of vasopressors in the emergency room has become a common practice. A recently published study investigated the incidence of human error and adverse hemodynamic events.

Push dose pressors were defined as:

• Phenylephrine (any dose)
• Epinephrine (<= 100 mcg) 

Adverse hemodynamic event was defined as:

• Extreme tachycardia (HR > 140 bmp)
• New bradycardia (HR < 60 bmp)
• Hypertension (SBP > 180 mmHg)
• Ventricular tachycardia

249 out of 1522 patients were identified and analyzed from Jan 2010 to November 2017

• median initial epinephrine dose (20 mcg; IQR: 10-100; range 1-100)
  • recieved more than one dose: 78 (57%)
• median initial phenylephrine dose (100 mcg; IQR: 100-100; range 25 to 10,000)
  • received more than one dose: 62 (56%)

Adverse event

• Phenylephrine group (n=110): 30 (27%; 95% CI: 19-36%)
• Epinephrine group (n=139): 68 (50%; 95% CI: 41-58%)

Errors

• Human error: 47 (19%) - similar proportion of human error between two agents.
• Dosing error: 7 (3%; 2.5 to 100-fold)
• Documentation error: 43 (17%)
• Only one dosing error occurred when a pharmacist was present

Conclusion

• Human errors and adverse hemodynamic event were common when “push dose pressors” were administered.
• Consultation with a pharmacist can/may reduce dosing error.

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Volatile inhalants such as glue, lighter fluid, spray paint are abused by "sniffing" (from container), "huffing" (poured into rag), or "bagging" (poured into bag). "Dusting" is the abuse of canned air dust removal products. These inexpensive easliy accessible products are so dangerous  that manufacturers include product warnings regarding lethal consequences from misuse and even may indicate that a bitterant is added to discourage use. Common duster gases include the halogenated hydrocarbons, 1,1-difluoroethane or 1,1,1-trifluroethane which are highly lipid soluble and rapidly absorbed by alveolar membranes and distributed to CNS. Desired effect of euphoria and disinhibition rapidly occur but unwanted side effects include confusion, tremors, ataxia, pulmonary irritation, asphyxia and, rarely, coma.

"Sudden sniffing death" is seen within minutes to hours of use and is due to ventricular arrhythmias and cardiovascular collapse. Available experimental evidence postulates the following mechanisms: Inhibition of cardiac sodium, calcium, and repolarizing potassium channels hERG and I(Ks) causing reduced conduction velocity and altered refractory period leading to reentry arrythmias or myocardial "sensitiization" to catecholamines resulting in after depolarizations and enhanced automaticity. Treatment should include standard resuscitation measures but refractory arrythmias to defibrillation have been reported and use of amiodarone and beta blockers should be considered.

Bottom Line:

• Volatile Inhalant Abuse is common and dangerous 
• SSD can occur even with first use
• Ventricular arrythmias can be refractory to electricity. Consider amiodarone and beta blockers.

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Cyanide poisoning, while uncommon, is frequently fatal. Current antidotes include methemoglobinemia inducers (nitrites), sulfur donators (thiosulfate), and hydroxocobalamin. Each has risks and benefits that must be considered. Three new potential antidotes, including sodium tetrathionate, have recently been evaluated in swine models.

 
Intramuscular sodium tetrathionate¹

• Sodium tetrathionate can bind and eliminate two cyanide molecules compared to one cyanide molecule by thiosulfate.
• Studied in a large (50 kg) female swine model of cyanide poisoning.
• All pigs were given cyanide via IV until 6 minutes post-onset of apnea, then given an approximately 1.5 mL IM injection of sodium tetrathionate (18 mg/kg).
• Survival at 90 minutes was 100% (6/6) in the treated group and 16% in the control arm (1/6). 

Advantages:

• Small volume injection (~1.5-2 mL in humans)
• No interference with routine laboratory tests.
• Ease of administration in pre-hospital or potential mass casulty setting.

Bottom line:

• New cyanide antidotes are being developed.
• The FDA does NOT require human trials of efficacy for cyanide antidotes.
• It is unclear where these drugs are in the approval process at this time, but look for them in the future.

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Naloxone distribution programs have been expanding to promote the naloxone adminstration by laypersons, usually intranasal (IN) device, to victims of opioid overdose. A recent study analyzed the reports of prehospital naloxone administration reported to a regional poison center.

• 1139 cases of prehospital naloxone administrations were identified between 2015 and 2017.
• 98.2% had ventilatory depression
• 97% were unresponsive
• Law enforcement officers administered 91% of the naloxone, 97.9% via IN route

Opioid toxicity revesal:

• Opioid-induced ventilatory or CNS depression was reversed in 79.2% after administering a mean naloxone dose of 3.12 mg. 
• EMS administered additional naloxone (mean dose: 2.2 mg) to 291 due to lack of or partial reversal of opioid toxicity. 
• 254 out of 291 (92.4%) regained normal/improved mental and ventilatory status.  
• 95.9% of the overdose victims survived.

However, between 2015 and 2017, the reversal rate decreased (82.1% to 76.4%) while mean administered naloxone dose increased (2.12 mg to 3.63 mg). The cause of this trend is unknown but the dose of commercially available IN naloxone kit increased from 2 mg to 4 mg in 2016.

Bottom line:

• IN naloxone administration is an effective intervention to reverse opioid toxicity.
• However, larger naloxone doses were administered between 2015 and 2017 while the reversal rate decreased.
• It is essential for bystander/witness of overdose to notify EMS as overdose victims may require additional naloxone administration/medical attention.

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Since 2013, the availability of fentanyl has been increasing in the illicit drug supply, especially in heroin supply. Fentanyl and its analogs have been responsible for the dramatic increase in opioid overdose death over the past 5 years. 

Two recent cross-sectional studies screened ED patients with opioid use disorder for fentanyl exposure.

Study 1:

• Of 165 patients, urine samples were obtained from 129 participants.
• 80.6% tested positive for fentanyl from urine sample when over 95% reported preference for heroin in the fentanyl positive group.
• 85.7% of the overdose group (n=42) was positive for fentanyl.
• Over 84% recognized fentanyl’s high potency and high risk of death in overdose.
• 29.7% (n=49 of 165) intentionally purchased fentanyl for use.  
• Intentional fentanyl purchase was more common in non-overdose group(34.1% vs. 16.7%).

Study 2: 

• 76 ED patients were screened.
• 83% showed presence of fentanyl in urine.
• 5% reported knowledge of using fentanyl (i.e. intentional use).

Bottom line:

• Fentanyl exposure is common among opioid users in Baltimore
• Up to 30% of ED patients with opioid use disorder intentionally purchase fentanyl although majority recognize the higher risk of overdose death from fentanyl compared to other opioids.

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Many chemicals and substances - both legal and illegal - can be purchased from an online retailer. A recent study searched Amazon.com to see if any of the "extremely hazardaous substances" identified by Environmental Protection Agency (EPA) were available for purchase.

Amazon.com was searched over 10-month period.

Result:

• 79 of 340 substances listed as "extremely hazardous by the EPA were available for purchse. 
• 1/3 of the products/substances possess sufficient dose to be considered toxic in single unit purchase
• Only 4 substances required a bussiness account to be purchase. 

Bottom line:

Toxic substances are readily available from many online retailers that can potentially cause serious toxicity. Online retailers should consult with experts and governmental agencies to limit the availability of such products.

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