Fatalities related to new psychoactive substances in Singapore-A case series.

The use of New Psychoactive Substances (NPS) has become a serious global issue with increasing number of reports of their toxicities and fatalities. Likewise, in Singapore, the number of exhibits containing NPS detected had increased 80% from 2011 to 2014. This is a case series of the first four autopsy cases of fatalities due to or related to the use of NPS in Singapore. In one case, we present the first reported case of death due directly to ADB-FUBINACA toxicity (post-mortem blood concentration of 56ng/ml). Another case was due to 25B-NBOMe toxicity (post-mortem blood concentration of 10ng/ml) while the last two cases were deaths related to 5-Fluoro ADB, where the metabolites of the drug were detected.

Fatal intoxication of a regular drug user following N-ethyl-hexedrone and ADB-FUBINACA consumption.

In Hungary, N-ethyl-hexedrone (NEH) was the most frequently seized stimulant designer drug in 2017, while among synthetic cannabinoids ADB-FUBINACA and AB-FUBINACA were the most popular. Symptoms of intoxication by these substances are well known but less is known about the pathology of overdose-related death. NEH-induced fatal intoxication has not been described in the literature and knowledge surrounding the particular circumstances of death could be useful better public education of risk and more adequate treatment of overdose patients. In this report, we characterize the case of a 23-year-old male regular drug user who died a few hours after NEH and ADB-FUBINACA consumption. His medical history showed arrhythmia in childhood, and some seizures. Autopsy found he had a BMI of 42.9, a hypertrophic and dilated heart, severe atherosclerosis of the valves, coronaries and the arteries, and edema of the internal organs. Histology confirmed those findings. Postmortem blood levels of NEH were 285 ng/ml, along with 0.08 ng/ml ADB-FUBINACA and five ADB-FUBINACA metabolites. Based on the blood concentrations measured in suspected drug users (≤83.9 ng/ml) we hypothesize that NEH intoxication was the cause of death in this case, with heart disease being a co-factor and that the synthetic cannabinoid effect might have been accompaniment. This case also offered the opportunity to identify the metabolites of ADB-FUBINACA in the blood. We identified metabolites in the post-mortem blood by comparing them to human liver microsomal enzyme metabolites in vitro. Three major and two minor metabolites were found in the blood, of which two could only be derived from ADB-FUBINACA, as opposed to other cannabinoids. The case highlights the importance of the complex analysis of drug related deaths by medico-legal autopsy, histopathology and toxicology.

Fatal intoxication with new synthetic cannabinoids AMB-FUBINACA and EMB-FUBINACA.

Introduction: Synthetic cannabinoids are currently the largest group of new psychoactive substances. Those that have been subjected to legal control are replaced by newer uncontrolled substances, which causes constant and dynamic changes to the drug market. Some of the most recent synthetic cannabinoids that have appeared on the "legal highs" market are AMB-FUBINACA and EMB-FUBINACA. Case history: A 27-year-old man was found dead on a bed in an apartment. At autopsy, congestion of internal organs, pulmonary oedema and left-sided pleural adhesions were found. The medical examiner concluded that the man died due to acute respiratory failure. The autopsy materials (blood, urine, liver, kidney, stomach, intestine, lung and brain) were collected for further toxicological analyses. Methods: The synthetic cannabinoids AMB-FUBINACA and EMB-FUBINACA were isolated from autopsy materials by precipitation with acetonitrile. The quantitative analyses were carried out by LC-MS/MS. Results: AMB-FUBINACA and EMB-FUBINACA were detected and quantified in all post-mortem materials except the blood. The determined concentrations of these compounds in solid tissues were in the range of 0.2-0.9 ng/g and 0.2-3.5 ng/g. The highest concentrations of AMB-FUBINACA and EMB-FUBINACA were revealed in the stomach content (5.8 and 36.2 ng/mL, respectively). Discussion: The presented case demonstrates that even in cases of fatalities, it is possible that the parent substance will not be present in the blood, while being present in other autopsy materials. The determined concentrations of the compounds may indicate oral administration of synthetic cannabinoids. It can also be assumed that AMB-FUBINACA and EMB-FUBINACA probably contributed to death. Conclusion: The presented case shows that synthetic cannabinoids can be undetected in the blood of even seriously or fatally intoxicated people. This situation means that the analysis of only blood samples may not confirm poisoning. The presented case also suggests that AMB-FUBINACA and EMB-FUBINACA use is dangerous to health and may lead to fatal intoxication.

A case of intoxication with a mixture of synthetic cannabinoids EAM-2201, AB-PINACA and AB-FUBINACA, and a synthetic cathinone α-PVP.

We report a case of intoxication with a mixture of three synthetic cannabinoids and a synthetic cathinone, which have been disclosed by a highly sensitive progressing technology. A man was found dead, and his forensic autopsy was performed at our department. After further examinations of his specimens, EAM-2201 and α-PVP have been newly found in his lung. The concentrations of EAM-2201 have not been reported yet in any authentic human specimens although its existence (not quantified) in blood was reported in 2015. Therefore, a sensitive quantitation method of these compounds in blood and solid tissues has been devised using the sensitive instrument. The limits of detection of these compounds were in the range of 3-10 pg/ml with their quantification range of 10-1000 pg/ml in blood. The femoral vein blood levels of EAM-2201 and AB-PINACA were 56.6 ±â€¯4.2 and 12.6 ±â€¯0.1 pg/ml, respectively, and AB-FUBINACA could be detected but not quantifiable in the blood specimens; α-PVP could not be detected. The standard addition method was employed for the quantification of these compounds in the lung, liver and kidney specimens. The lung levels of EAM-2201, AB-PINACA, AB-FUBINACA and α-PVP were 348 ±â€¯34, 355 ±â€¯30, 124 ±â€¯12 and 59.0 ±â€¯7.4 pg/g, respectively. In conclusion, in this study, the concentrations of EAM-2201 in authentic human specimens including blood and solid tissues and those of AB-PINACA and AB-FUBINACA in solid tissue specimens were quantified for the first time to our knowledge.

Coma, Seizures, Atrioventricular Block, and Hypoglycemia in an ADB-FUBINACA Body-Packer.

BACKGROUND: Synthetic cannabinoid intoxication has become difficult to diagnose and manage in the United States, in part due to varying clinical effects within this heterogeneous group of compounds. CASE REPORT: A 38-year-old man was admitted with altered mental status and bradycardia. He demonstrated progressive encephalopathy, seizure activity, second-degree atrioventricular block type I, respiratory failure, hypotension, hypothermia, and hypoglycemia. A computed tomography scan of the abdomen and pelvis revealed multiple packages in the patient's stomach and rectum. Multiple attempts at gastrointestinal decontamination were unsuccessful. On hospital day 8 the patient developed hypertensive emergency and was taken to the operating room for exploratory laparotomy. Twenty-two poorly wrapped packages were removed from the bowel. Postoperatively the patient demonstrated both generalized and focal seizure activity. His mental status slowly returned to baseline over the period of about 1 week and he was ultimately discharged without neurological sequelae after 1 month. Analysis of patient serum, urine, and plant matter from the packages identified cannabis and 2.N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (ADB-FUBINACA). WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The case presented demonstrates the suspected toxidrome associated with severe ADB-FUBINACA intoxication, including mental status depression, bradycardia, autonomic instability, seizure, hypoglycemia, and hypothermia. Although the patient had simultaneous exposure to cannabis, his constellation of symptoms is not consistent with cannabis intoxication. A previous animal model supports the potential of this specific synthetic cannabinoid to cause the reported toxidrome.

Acute side effects after consumption of the new synthetic cannabinoids AB-CHMINACA and MDMB-CHMICA.

INTRODUCTION: In 2014, the "European Monitoring Centre for Drugs and Drug Addiction" (EMCDDA) reported on 30 novel synthetic cannabinoids (SCs). Among these were indole- and indazole-based valine derivatives with a cyclohexylmethyl side chain (e.g., AB-CHMINACA and MDMB-CHMICA), which represent a new class of SCs. METHODS: A prospective observational study of patients treated in emergency departments (EDs) after the intake of SCs was conducted. Clinical and laboratory data were combined and reported to a poison control centre. Serum and/or urine samples of ED patients were analyzed using LC-MS/MS. RESULTS: Forty four patients (39 male, five female, 12-48 years) were included. AB-CHMINACA (MDMB-CHMICA) was identified in 20 (19) serum samples, and in 21 (25) urine samples, respectively. In 19 of the cases, more than one SC was present. Other psychoactive substances (mainly amfetamines) were identified in seven cases, but in five out of these in urine samples only. Based on the Poison Severity Score, severity of poisoning was minor (4), moderate (31) or severe (9). Most frequently reported neuropsychiatric symptoms were CNS-depression (n = 21, 61%), disorientation (n = 20, 45%), generalized seizures (n = 12, 27%), combativeness (n = 8, 18%) and extreme agitation (n = 7, 16%). Duration of symptoms lasting 24 hours or longer occurred in 15 cases (34%). DISCUSSION: The prevalence of certain neuropsychiatric symptoms was higher in our study than in former reports after the intake of SCs of the aminoalkylindole-type (first generation) SCs. In addition, severe poisoning and duration of symptoms were also higher. CONCLUSIONS: In this study, the valine derivative AB-CHMINACA and the tert-leucine derivative MDMB-CHMICA ("third generation of SCs") seem to be associated with more severe clinical toxicity than was previously reported in patients exposed to earlier generation SCs such as JWH-018. However, this observation needs to be confirmed with a larger cohort of patients with analytically confirmed abuse of third generation SCs. The rapid turnover of SCs on the drug market together with the occurrence of SCs such as AB-CHMINACA and MDMB-CHMICA is alarming, especially because of the unexpectedly high frequency of neuropsychiatric symptoms.

Intoxication from the novel synthetic cannabinoids AB-PINACA and ADB-PINACA: A case series and review of the literature.

Synthetic cannabinoids (SC), are a novel class of designer drugs which emerged as a drug of abuse in the late 2000's. We report a case series of 6 patients who may have smoked a synthetic cannabinoid product in a remote wilderness setting. They presented with varying degrees of altered mental status, agitation, and seizures. Two were confirmed to have AB-PINACA, ADB-PINACA and their respective pentanoic acid metabolites in biological specimens via liquid chromatography time-of-flight mass spectrometry (LC-TOF/MS). Both compounds had DEA Schedule I classification at the time of case presentation, and 22 SCs are currently temporary or permanent DEA Schedule I. More than 150 SCs are known to date, and new compounds are appearing at a rapid rate on darknet and surface web e-commerce websites, marketed as "research chemicals" or "legal highs." The scale and rapidity of SC evolution make legal control and analytical detection difficult. Nontargeted testing with liquid chromatography high resolution mass spectrometry (LC-HRMS), examining both parent compounds and metabolites, is the ideal method for novel SC identification and confirmation. Due to full agonism at the cannabinoid receptors CB1 and CB2, clinical effects are more severe than marijuana, which is a partial cannabinoid receptor agonist. They include agitated delirium, lethargy and coma, seizures, tachycardia, hypertension, and hallucinations, among other findings. Treatment is primarily symptomatic and aimed at airway protection and control of agitation and seizures. SCs do not appear to be abating anytime soon and require the cooperation of law enforcement, analytical scientists, and clinicians to adequately control. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.'

AB-CHMINACA-induced sudden death from non-cardiogenic pulmonary edema.

CONTEXT: Despite widespread use of diverse synthetic cannabinoid (sCB) compounds, the pathophysiology associated with intoxication with many sCB compounds, including AB-CHMINACA, is poorly understood, as is their metabolism and distribution into blood and organs. CASE DETAILS: A young man died shortly after ingesting an herb product containing sCB compounds. Toxicological analyses of blood samples revealed high levels of AB-CHMINACA (7.61 ± 0.59 ng/mL) and its metabolites (M2, 56.73 ± 4.16 ng/mL; M4, 2.29 ± 0.14 ng/mL) and trace amounts of 5-fluoro-AMB, FUB-PB-22, and AB-FUBINACA. The autopsy revealed severe pulmonary edema, and histology showed air bubbles in the alveolar effusion, suggesting rapid progression of edema. Low blood levels of N-terminal pro-brain natriuretic peptide excluded cardiogenic pulmonary edema. Histological examination revealed diffuse neuronal (brain) and myocardial (sub-endocardial) hyper-eosinophilia, indicating hypoxic encephalopathy and systemic hypoxemia, respectively. CONCLUSIONS: The findings show that AB-CHMINACA induced rapid progression of pulmonary edema resulting in hypoxic encephalopathy and systemic hypoxemia, possibly through severe seizures. The high blood ratio of the M2 metabolite to the parent compound, AB-CHMINACA, demonstrates rapid metabolism. This highlights the usefulness of quantification of M2 in diagnosing AB-CHMINACA intoxication.

Aspects related to analysis and medico-legal assessment in the context of the presence of synthetic cannabinoids in biological material based on the example of AB-CHMINACA.

AIM OF THE STUDY: The aim of this study was to develop and validate a method for the determination of the synthetic cannabinoid AB-CHMINACA in blood, followed by its verification in forensic toxicological practice. MATERIAL AND METHODS: The case of a 41-year-old man admitted to hospital because of scheduled cardiac surgery was discussed. The man died after 12 hours of hospitalization. Based on collected evidence, AB-CHMINACA poisoning was suspected. The identification and determination of AB-CHMINACA in the man's blood was performed by high-performance liquid chromatography coupled with tandem mass spectrometry using electrospray ionization (HPLC-ESI-MS-MS), after prior solid phase extraction. RESULTS: The concentration of AB-CHMINACA determined in the man's blood sample was 0.5 ng/ml. CONCLUSIONS: In the interpretation of the case, it was concluded that AB-CHMINACA had no direct effect on the patient's death, the cause of which was ascertained as chronic heart failure secondary to aortic valve disease, decompensated by pneumonia. However, an indirect impact of side effects resulting from the use of synthetic cannabinoids cannot be ruled out. They might have exacerbated the man's disease process leading to sudden cardiac arrest caused by asystole.

Supraventricular tachycardia and acute confusion following ingestion of e-cigarette fluid containing AB-FUBINACA and ADB-FUBINACA: a case report with quantitative analysis of serum drug concentrations.

BACKGROUND: AB-FUBINACA and ADB-FUBINACA are structurally similar synthetic cannabinoids with potent CB1 receptor agonistic effects. Very little is known about their pharmacology and toxicology. OBJECTIVE: To report a case of supraventricular tachycardia and acute confusion after ingestion of e-cigarette fluid containing AB-FUBINACA and ADB-FUBINACA, with quantitative analysis of the serum drug concentrations. CASE REPORT: A healthy 24-year-old man ingested two drops of e-cigarette fluid which were later found to contain AB-FUBINACA and ADB-FUBINACA. Within 30 min of ingestion, he became somnolent, confused, and agitated, with palpitation and vomiting. On arrival to the emergency department, a short run of supraventricular tachycardia was noted, which resolved spontaneously. Bedside urine immunoassay failed to detect recreational drugs. Laboratory blood tests showed mild hypokalemia. Exposure to AB-FUBINACA and ADB-FUBINACA was confirmed analytically, with serum concentrations of 5.6 ng/mL and 15.6 ng/mL, respectively, in the blood sample collected on presentation. The patient recovered uneventfully with supportive treatment and was discharged 22 h after admission. DISCUSSION: AB-FUBINACA and ADB-FUBINACA are orally bioavailable with rapid onset of toxicity after ingestion. In this case, supraventricular tachycardia was likely the result of exposure to AB-FUBINACA and ADB-FUBINACA. The serum concentrations of AB-FUBINACA and ADB-FUBINACA were higher than those previously reported in fatal cases. CONCLUSION: In the context of acute poisoning, the presence of unexplained tachyarrhythmias, confusion, and a negative recreational drug screen should prompt clinicians to consider synthetic cannabinoid toxicity as a differential diagnosis.

Occupational transdermal poisoning with synthetic cannabinoid cumyl-PINACA.

CONTEXT: Synthetic cannabinoids are getting more popular among young people and illicit manufacturers. We report a case series of occupational transdermal poisoning with synthetic cannabinoids. CASE DETAILS: Three customs inspectors got in contact with a sticky substance with their fingertips because they were not wearing protection gloves and the delivered package was damaged. Despite washing their hands with water, signs of synthetic cannabinoids intoxication started occurring half an hour after exposure. On arrival at the Emergency Department six hours later, they were somnolent, lethargic and confused. They showed signs of mydriasis, blurred vision, ataxia, weakness, numbness, tachycardia and one of them had orthostatic hypotension. Two days later, they were feeling much better and reported amnesia and slowed perception of time after exposure. Toxicology analysis by LC-MS/MS revealed synthetic cannabinoid cumyl-PINACA (SGT-24) in their blood samples taken on admission. cumyl-PINACA was also confirmed with NMR method in liquid samples seized at the airport. It was 98% pure substance with the purpose of being diluted and sold further in the drug market by drug dealer. DISCUSSION: This case series highlights the possible transdermal exposure to synthetic cannabinoids oil resulting in prolonged cannabinoid syndrome.

Acute Toxicity Associated with Use of 5F-Derivations of Synthetic Cannabinoid Receptor Agonists with Analytical Confirmation.

INTRODUCTION: Synthetic Cannabinoid Receptor Agonists (SCRAs) are the largest group of new psychoactive substances reported to the European Warning System and the United Nations Office on Drugs and Crime to date. The heterogeneous nature and speed of diversification of these compounds make it challenging to accurately characterise and predict harms of these compounds in pre-clinical studies, ahead of their appearance. CASE REPORT: We report the case of a 19-year-old female who purchased three products from a headshop: two new psychoactive substances (sachets of "cannabis tea" and "mushroom tea") as well as two LSD blotters. After the "cannabis tea" was smoked and the two LSD blotters and "mushroom tea" were ingested, the patient became tachycardic (HR 128), developed seizures, agitation, visual hallucinations as well as suspected serotonergic toxicity (sustained ankle clonus 20-30 beats) 1-2 hours after use. She was treated with 1 mg of intravenous midazolam. Symptoms/signs resolved within 13 hours. No further supportive care was required. Plasma, blood, and urine samples confirmed the presence of two SCRAs: 5FAKB-48 and 5F-PB-22. The patient also reported therapeutic use of both fluoxetine and citalopram for depression. DISCUSSION: To the best of our knowledge, this is the first case report of non-fatal intoxication with 5F-AKB-48 with analytical confirmation and exposure times. It also highlights the difficulties in understanding the pattern of toxicity of certain SCRAs in the context of psychotropic medications/co-morbid mental illness.

Case Series of Synthetic Cannabinoid Intoxication from One Toxicology Center.

Synthetic cannabinoid use has risen at alarming rates. This case series describes 11 patients exposed to the synthetic cannabinoid, MAB-CHMINACA who presented to an emergency department with life-threatening toxicity including obtundation, severe agitation, seizures and death. All patients required sedatives for agitation, nine required endotracheal intubation, three experienced seizures, and one developed hyperthermia. One developed anoxic brain injury, rhabdomyolysis and died. A significant number were pediatric patients. The mainstay of treatment was aggressive sedation and respiratory support. Synthetic cannabinoids pose a major public health risk. Emergency physicians must be aware of their clinical presentation, diagnosis and treatment.

Acute intoxication of four individuals following use of the synthetic cannabinoid MAB-CHMINACA.

CONTEXT: The largest group of new psychoactive substances (NPS) are synthetic cannabinoids (SC). Those that become controlled are immediately replaced by new uncontrolled substances. The recent resurgence of the NPS market in Poland resulted in a further amendment to the Drug Addiction Counteraction Act. This resulted in significant changes in the composition of "legal high" preparations, and consequently a large outbreak of intoxications with SC was reported in Poland at the beginning of July 2015. CASE DETAILS: This paper describes the circumstances of intoxication and toxicological findings in an acute intoxication of four individuals with MAB-CHMINACA. They each smoked tobacco mixed with powder from the package with the description "AM-2201". The adverse effects observed in the individuals included vomiting, seizures, limb twisting, muscle tremors, aggression, agitation, slurred speech, blood pressure spikes, wheezing, respiratory failure and losses of consciousness. Blood samples were analysed using liquid chromatography with mass spectrometry. Results from analysis performed on the blood samples showed the presence of MAB-CHMINACA, while AM-2201 was not found (LOD 0.09 ng/mL). The determined concentrations were 5.2, 1.3, 1.7 and 14.6 ng/mL, respectively. The analyses of the blood did not reveal any other substances (excluding medicines given in hospital). CONCLUSION: The presented cases show the health risks associated with MAB-CHMINACA use and confirm that "legal high" preparations do not always contain a substance represented on the package.

Death Associated With the Use of the Synthetic Cannabinoid ADB-FUBINACA.

Synthetic cannabinoids have been found in herbal incense products for the last several years. We report the rapid death of an individual that was certified as synthetic cannabinoid-associated. The autopsy blood specimen was extracted by a liquid-liquid extraction at pH 10.2 into a hexane-ethyl acetate mixture and analyzed by a generalized synthetic cannabinoid LC-MS-MS method. For this case report, we briefly describe the instrumental analysis and extraction methods for the detection of ADB-FUBINACA in postmortem blood, toxicological results for the postmortem blood specimen (ADB-FUBINACA, 7.3 ng/mL; THC, 1.1 ng/mL; THC-COOH, 4.7 ng/mL), case information and circumstances and pertinent findings at autopsy. The cause of death was certified as coronary arterial thrombosis in combination with synthetic cannabinoid use. Manner of death was accident.

Identification and quantification of metabolites of AB-CHMINACA in a urine specimen of an abuser.

We experienced an autopsy case in which the cause of death was judged as poisoning by multiple new psychoactive substances, including AB-CHMINACA, 5-fluoro-AMB and diphenidine [Forensic Toxicol. 33 (2015): 45-53]. Although unchanged AB-CHMINACA could be detected from 8 solid tissues, it could neither be detected from blood nor urine specimens. In this article, we obtained eight kinds of reference standards of AB-CHMINACA metabolites from a commercial source. The AB-CHMINACA metabolites from the urine specimen of the abuser were extracted by a modified QuEChERS method and analyzed by liquid chromatography-tandem mass spectrometry before and after hydrolysis with ß-glucuronidase. Among the eight AB-CHMINACA metabolites tested, only 2 metabolites could be identified in the urine specimen of the deceased. After hydrolysis with ß-glucuronidase, the concentrations of the two metabolites were not increased, suggesting that the metabolites were not in the conjugated forms. The metabolites detected were 4-hydroxycyclohexylmethyl AB-CHMINACA (M1), followed by N-[[1-(cyclohexylmethyl)-1H-indazol-3-yl]carbonyl]-l-valine (M3). Their concentrations were 52.8 ± 3.44 and 41.3 ± 5.04 ng/ml (n=10) for M1 and M3, respectively. Although there is one preceding report showing the estimations of metabolism of AB-CHMINACA without reference standards, this is the first report dealing with exact identification using reference standards, and quantification of M1 and M3 in an authentic urine specimen.

A Common Source Outbreak of Severe Delirium Associated with Exposure to the Novel Synthetic Cannabinoid ADB-PINACA.

BACKGROUND: Since 2009, synthetic cannabinoid (SC) use has emerged as a growing public health threat in the United States (US). Several outbreaks of unexpected, severe toxicity linked to SC use have been reported since 2012. Reports of varied and significant morbidity after SC use are expected to increase because newer compounds enter the marketplace more frequently as manufacturers attempt to circumvent regulatory efforts. CASE REPORT: We report a cluster of 7 patients who experienced a spectrum of anxiety, delirium, psychosis, and aggressive behaviors after smoking the same SC-containing product at a party. An 8th patient with the same exposure source presented with delayed onset seizures. Biologic samples were analyzed for novel, newly identified SCs belonging to the FUBINACA family of compounds. A previously unknown SC, N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide (ADB-PINACA) was identified in biologic samples from 7 of the individuals. ADB-PINACA was identified in the SC-containing product ("Crazy Clown") seized by law enforcement and identified as the product smoked by the 8 patients in the reported cluster. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The information compiled using this cluster of cases, and a similar reported outbreak of altered mental status in Colorado, implicating the same SC (ADB-PINACA) and brands of SC-containing products, aided the US Drug Enforcement Administration in its temporary scheduling of ADB-PINACA and three other SCs. In this outbreak, close cooperation between public health and law enforcement allowed for a rapid intervention, which halted the outbreak by interrupting the common source and accelerated regulatory efforts to prevent further morbidity and mortality.